Transgenic Research 6, 309±319 (1997)

Rules and guidelines for genetic nomenclature in mice:

excerpted version

C O M M I T T E E O N S TA N DA R D I Z E D G E N E T I C N O M E N C L AT U R E
FOR MICE
C h a i r p e r s o n : M U R I E L T. DAV I S S O N
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA

Received April 14 1997; accepted 18 April 1997

The unique identification of genes and mouse strains is critical to their identification in research and in the
scientific literature. Rules for genetic nomenclature in mice have existed since the 1940s. The latest complete
revision of the rules was approved by the International Committee on Standardized Genetic Nomenclature for Mice
in November, 1993. Minor revisions have occurred since. The complete, current rules are available on-line from
The Jackson Laboratory's Mouse Genome Database (MGD), URL: http://www.informatics.jax.org. A printed
version appeared in Mouse Genome 92 (2), June, 1994, and in Genetic Variants and Strains of the Laboratory
Mouse, 3rd edition (Committee on Standardized Genetic Nomenclature for Mice, 1996a,b,c). The excerpted version
below gives the general guidelines for naming and symbolizing mouse genes, transgenes and transgenic strains,
targeted mutations and DNA markers. More detailed guidelines, including revisions as they are made, may be
found at the MGD Web site given above. Subparagraphs are numbered as in the complete guidelines so that the
user can refer easily from this excerpted version to the full text. Textual references to paragraphs not included here
may be found in the full text as well.

1. General rules for gene nomenclature
Introduction
Gene nomenclature guidelines are based upon the premise
that the primary purpose of a gene or locus symbol is to
provide a brief and universally acceptable symbol that
uniquely identifies a specific gene or locus; all other
purposes of a symbol are secondary and should not
interfere with this primary purpose.
1.1.1. Names of genes or loci
Names of genes and loci should be brief and chosen to
convey as accurately as possible the character by which
the gene is usually recognized. Genes are functional units,
whereas a locus can be any distinct, recognizable DNA
sequence (see 1.1.3).
1.1.2. Symbols for genes
1. Symbols for genes should typically be two-, three-,
or four-letter abbreviations of the name. Hyphens are
0962±8819 # 1997 Chapman & Hall
used in gene symbols only for clarity, primarily to
separate characters that together might be confusing, e.g.:
(1) two numbers that would be in adjacent positions,
such as Lamb1-2,
(2) -rs and - ps (related sequence and pseudogene,
respectively, see 1.1.4) from gene symbols,
(3) as required, characters for loci in a complex from
the complex symbol (see 1.1.12 and 1.2.1),
(4) components of mutant allele symbols, such as
Mod1a-m1Lws (see 1.1.7.7).
2. The total number of characters in a locus symbol
should not exceed 10 unless this maximum limit would
cause violation of some other rule.
3. Except in the case of loci first discovered because
of a recessive mutation (see Section 1.1.7), the initial
letter of the locus symbol should be capital, and all
others lower case.
4. In published articles gene symbols should be set in
italics, e.g. dw, dwarf; Hbb, haemoglobin b-chain.
5. Identification of new loci should not be assumed
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from the discovery of variation, whether morphological,
biochemical, quantitative or antigenic.
6. A proposed new symbol must never duplicate one
already used for another locus. Date of publication in a
refereed journal, provided the symbol is acceptable,
establishes priority. Symbols for new loci can be reserved
through the MGD at The Jackson Laboratory, Bar
Harbor, Maine, USA.
7. When a well-known locus has been recognized
initially by a mutation and later the structural locus is
identified, the locus is identified by the symbol for the
structural locus and the mutant allele symbol is
designated as a superscript to the structural locus symbol,
e.g. W, which is a mutation in Kit, becomes Kit W .
8. Symbols for quantitative trait loci (QTL) genes shall
follow the rules for other types of genes (see 1.1.1). They
should be symbolized with 3-4 character symbols that are
acronyms of the name and begin with a capital letter.
Those affecting the same complex trait, i.e. in a series
like Idd loci, shall be given the same stem symbol and
serially numbered. `q' may be used as the final letter
preceding the serial number but is not required.
9. Expressed sequence tagged (EST) loci, when
mapped to chromosomes, may be given either D symbols
with a final `e' for expressed or the symbol ESTM###,
where M identifies mouse as opposed to human EST loci
and ### ˆ a serial number assigned from the Mouse
Genome Database (MGD).
10. Genes encoded by the opposite (antisense) strand
of a known gene shall be given their own symbols.
11. Alternative transcripts from the same gene should
not be given different `locus' symbols.
12. For homologous genes, to facilitate comparative
mapping one should use the mouse equivalent of the
symbol already adopted for the conserved gene in other
species. For example, the gene symbol for amyloid beta
precursor protein is APP in the human and cow genomes
and App in the mouse. If the exact symbol has already
been assigned to another gene in the mouse, the symbol
should be modified to one resembling as closely as
possible that used in the other species; e.g. by adding a
single letter such as `h' for homologue. One should also
try not to duplicate a symbol used for a different gene in
another species. Do not insert the letter `m' or `M' (for
mouse) as the first letter of the symbol for a locus with
homologues in other species.
1.1.3. Genes and loci recognized by DNA sequence
A gene, including both transcribed DNA sequences and
associated regulatory elements, can span a considerable
length of chromosomal DNA. Sequences at many places
in a gene might, therefore, vary from strain to strain of
mouse, and each variation could be any of several kinds:
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point substitutions, insertions or deletions (e.g. of retro-
viral elements), and variations in simple sequence repeat
numbers. Each such variant has the potential to define a
distinct genetic locus or DNA segment, given a specific
assay and appropriately recombinant mice, and the full set
of variants possessed by any given form of gene or length
of chromosomal DNA defines a haplotype. The term
haplotype is also used to define a complement of alleles at
multiple loci within a complex (see Sections 1.2.1 and
1.2.3).
To describe the results of a DNA typing assay
unambiguously, investigators should, therefore, give the
gene name and symbol, the assay (e.g. probe or PCR
primers, and restriction enzyme if any), and, if a specific
DNA segment within the gene is being assayed, the D
locus symbol. An important function of chromosome
committees and of databases is to assemble such data to
define haplotypes for genes. To avoid ambiguity, assay
names and probe names should not resemble D symbols;
use of the letter `D' should be reserved for DNA loci.
D symbols are used in two ways:
1. Loci recognized by anonymous DNA probes should
be given D symbols. This use of D symbols as gene or
locus symbols should be reserved for anonymous DNA
loci distinct from known genes.
2. Intragenic loci may be given D symbols to
distinguish individual sites within a gene. Remember
that genes are functional units whereas loci can be any
distinct DNA segment, and that several variant D loci
may lie within, and be used to assay, a gene. Variation in
DNA sequence of a known gene or tightly linked
sequences should be described using the gene symbol
and current rules for nomenclature of genes and alleles.
Intragenic D locus symbols should only be used (a) when
describing intragenic mapping analysis or (b) when
stating that a gene was typed using an intragenic D
locus (see next paragraph for the most common example
of this).
Note: While D symbols could be given to all variants
within a gene, the Committee discourages the use of D
symbols for intragenic DNA segments except when a D
locus symbol is needed to relate a segment to other
objects within or near the gene. YAC ends may be given
D symbols when they are used for genetic mapping.
(Note approved November 1995).
Loci recognized by variation in copy number of mini-
or microsatellites should be given D symbols. If such
microsatellite (D symbol) loci are within or very near
known genes and, thus, can be used to detect those
genes, then the gene symbol should always be used to
refer to the gene, e.g. the gene's location on the
chromosome, and the D symbols should only be used
to refer to specific sites within the gene, e.g. to convey
Rules and guidelines for genetic nomenclature in mice: excerpted version
intragenic mapping information. When D symbol loci fall
within known genes, on general maps the gene will be
identified by the gene symbol and the locus (D) symbols
will appear in locus lists and databases cross-referenced
with the gene. Locus symbols would, of course, be used
on fine structure, high resolution maps around and within
genes.
D symbols are composed of four parts:
(1) D for DNA.
(2) 1 . . . 19, X and Y for the chromosomal assign-
ment, and 0 for unmapped loci.
(3) A 2±3 letter laboratory registration code indicating
the laboratory or scientist describing the locus. The same
symbol should be used for a laboratory's loci, chromo-
some aberrations, and inbred substrains, e.g. Pas for
Pasteur Institute. A code can be obtained from the central
registry maintained by the Institute of Laboratory Animal
Resources (see section on Laboratory Registration Codes
below).
(4) A unique serial number. It is preferred that
numbers be assigned to loci in the order the loci are
described on each chromosome for a particular labora-
tory, e.g. D1Pas5 the fifth D locus developed and
mapped on Chromosome 1 at the Pasteur Institute. The
use of a number from the probe that detects the locus,
e.g. D17Leh48, a Chromosome 17 D locus identified by
probe number Tu48 of Lehrach, is discouraged.
Recognizing that allelic variation detected by DNA probes
can be complex, the Committee proposes the following. In
published papers, the allele type of a specific strain should
be given by fragment(s) size with a description of the
assay used. When simple allele symbols are required, as
for display of linkage data or listing in databases or locus
lists, a single letter abbreviation for the strain should be
used (see Alleles, section 1.1.7.9). Allele symbols should
be written as a lowercase superscript when appended to
the locus symbol; in tables of linkage data in publications
a single uppercase letter denoting the strain may be used.
The assay or restriction enzyme must be specified for
each allele used in publication or entered into a database,
because the same two strains may differ with one assay
but be indistinguishable with another. That is, a strain may
have of as designating the haplotype for that gene or
segment of DNA (see Section 1.1.3, para. 1 and Section
1.1.7, general rules for allelic designation).
If an anonymous DNA locus identified only by the D
symbol is later identified to be a known locus or the
function of the gene is determined, the D symbol should
either be replaced by the known gene's symbol or
changed to a new gene symbol that is an acronym for the
new gene's name. If more than one mutation is identified
within the gene, the original D symbol should be retained
for the mutated site it originally designated (see Section
1.1.3, para. 3). If a D locus is shown to be expressed but
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its function remains unknown, a lower case `e' for
expressed should be added to the D symbol, e.g.
D1Pas5e. Newly identified expressed genes for which
the gene product is unknown should also be given D
symbols followed by `e'.
Anonymous DNA loci from the human genome that
cross-hybridize with mouse DNA and are mapped to a
mouse chromosome retain their human symbol in all
uppercase and the mouse chromosome number and a
capital H, for human, are inserted after the D, e.g.
D16H21S56 is a D locus on mouse Chromosome 16 that
cross-hybridizes with the probe for the 56th simple
sequence DNA locus from human Chromosome 21. This
same convention may be used for D loci derived from
other species. Single-letter abbreviations for other species
will be assigned by the International Nomenclature
Committee to assure that each letter unambiguously
indicates the species of origin. If a unique locus in
another species identifies more than one mouse locus, the
related sequence convention should be used (see 1.1.4).
Alternative or new loci detected with primers for a
known locus belong to the lab discovering them and shall
be symbolized by that lab with its lab code and next
serial number on the chromosome. `Mismapped' loci
should only be resymbolized if it can be proved that the
original locus does not exist in the original location.
B1 (and other types of) repeat `loci' should only be
given symbols if there is evidence of a unique locus (e.g.
genetic proof or polymorphism).
Xrf shall be used as the `lab code' in D symbols that
designate cross-referenced genes in mice and yeast or
other species. Symbols will be DChr#Xrf###, where ###
is a serial number assigned by the Johns Hopkins
database. Typically, a clone derived from yeast may hit
2 (or more) mouse loci. These will not require the -rs
nomenclature because the clone number in the symbol
will identify relatedness between loci on different
chromosomes. A hyphenated serial number shall be used
when two loci detected by the same clone are on the
same chromosome.
Chromosomal regions detected cytologically and by
RFLPs
At least five chromosomal regions can be detected by a
specific cytological staining method that reveals the whole
region or loci within the region can be detected with DNA
probes: centromeres, pericentromeric heterochromatin (C-
bands), nucleolus organizer regions (NORs), homoge-
neously staining regions (HSRs) and telomeres. Chromo-
somal nomenclature guidelines should be followed for
cytologically detected chromosomal regions and gene
nomenclature for genetic loci. While we recognize the
distinction blurs, please try to follow these guidelines;
contact a member of the International Nomenclature
Committee if in doubt. Hc# is the symbol for a
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cytologically detected C-band; loci recognized by DNA
polymorphisms is heterochromatin should be given D
locus symbols. Centromeres are designated by the symbol
Cen when detected cytologically or referred to as a unit. If
it becomes possible and necessary to distinguish loci or
segments within the centromere, these should be given D
locus symbols. Polymorphic loci within NORs are
symbolized Rnr#, where Rnr ˆ ribosomal RNA and
# ˆ the chromosome on which the locus is located. If
more than one Rnr locus on the same chromosome is
distinguished by genetic means, the loci should be serially
numbered in order of identification, e.g. Rnr1-1, Rnr1-2.
For homogeneously staining regions, HSR is incorporated
into a chromosome aberration symbol (see chromosome
guidelines) or a D symbol is assigned to the locus
amplified and Hsr is added when it is amplified, e.g.
D1Lub1Hsr. Related sequence nomenclature (rs#) will be
used for telomere sequence loci recognized by poly-
morphic variants with telomere sequences. Telomere
sequences detected by cytogenetic methods shall be
symbolized Tel# like other chromosomal `anomalies or
variants'.
Transgenes (Section 1.3 in the complete guidelines;
MGD; Committee 1996)
All DNA sequences that are experimentally and stably
introduced into the germline of animals are considered
transgenes. They are named according to the following
conventions, which were developed by an interspecies
committee sponsored by the Institute of Laboratory
Animal Resources (ILAR, 1992). Transgenic symbols
can be registered with TBASE at the Human Genome
Database (GDB) at Johns Hopkins (URL: http://
www.gdb.org/Dan/tbse/tbase.html).
1. A transgene symbol consists of three parts, all in
roman typeface, as shown below:
TgX(YYYYYY)#####Zzz
Where: TgX ˆ mode,
(YYYYYY) ˆ insert designation,
##### ˆ laboratory assigned number and
Zzz ˆ laboratory registration code
A. The mode, designates the transgene and always consists
of the letters `Tg' followed by a letter designating the
mode of insertion of the DNA: H for homologous
recombination, R for insertion via infection with a
retroviral vector, and N for nonhomologous insertion.
`Knockout' or directed mutation of a specific known gene
should be designated using standard allele symbol con-
ventions, (see below). Transgenic nomenclature is used for
homologous recombination insertions when homologous
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recombination is used as a mechanism to insert a
transgene and it is the transgene itself that is of primary
interest. The purpose of this designation is to enable the
user to identify it as a symbol for a transgene and to
distinguish between the three fundamentally different
organizations of the introduced sequence relative to the
host genome, not simply to indicate the method of
insertion or nature of the vector. To illustrate these
distinctions, examples are given below.
· Mice derived by infection of embryos with MuLV
vectors are designated TgR; mice derived by microinjec-
tion of MuLV DNA into zygotes are designated TgN.
· Mice derived from ES cells by introduction of DNA
followed by recombination with the homologous genomic
sequence are designated TgH; mice derived by random
insertion of the same sequence by nonhomologous
crossing over events are designated TgN.
B. The insert designation is a symbol for the salient
features of the transgene, as determined by the investi-
gator. It is always contained within parentheses and
consists of no more than 6 characters: letters (capitals,
or capitals and lower-case letters) or a combination of
letters and numbers. Insert designations longer than 6
characters may be used only if the insert designation and
the laboratory assigned number (C. a. below) together are
11 characters or less. Italics, super- or subscripts, internal
spaces, and punctuation should not be used. While the
choice of the insert designation is up to the investigator,
the following guidelines should be followed:
a. The insert designation should identify the inserted
sequence and indicate important features. Where the
insertion uses sequences from a named gene, it should
contain the standard symbol for that gene. Hyphens are
omitted when using hyphenated gene symbols. If the
gene symbol exceeds the spaces available, use the
beginning letters of the symbol. For example, Ins1
should be used within the symbols of transgenes
containing either coding or regulatory sequences from
the mouse insulin gene (Ins1) as an important part of the
insert designation. Gene symbols are not italicized when
incorporated into transgene symbols.
b. Avoid using symbols that are identical to other
named genes in the same species. For example, the use
of `Ins' to designate `insertion' would be incorrect.
c. Ideally two different gene constructs should not be
identified by identical insert designations.
d. To aid communication, standard abbreviations can
be used as part of the insert designation.
These presently include:
An anonymous sequence
Gen genomic
Im insertional mutation
Rules and guidelines for genetic nomenclature in mice: excerpted version
Nc noncoding sequence
Rp reporter sequence
Sn synthetic sequence
ET enhancer trap construct
Pt promoter trap construct
This list will be expanded as needed and maintained by
the Nomenclature Committee.
e. The insert designation should identify the inserted
sequence, not its location or phenotype.
C. Laboratory Assigned Number and Laboratory Registra-
tion Code is a number and letter combination that must
uniquely identify each independently inserted sequence. It
is formed of two parts:
a. The Laboratory Assigned Number is a number from
1 to 99 999 that is uniquely assigned by the laboratory to
each stably transmitted insertion. This assignment should
be done at the time germline transmission is confirmed.
The number can have some intra-laboratory meaning or
simply be a number in a series of transgenes produced by
the laboratory. The same number cannot be used more
than once by each lab.
b. The Laboratory Registration Code is uniquely
assigned to all laboratories originating transgenic animals,
DNA loci or inbred strains (see Laboratory Registration
Code section below).
2. The complete designation identifies the inserted site,
and provides a symbol for unique identification. When a
mutation that produces an observable phenotype is caused
by the insertion, the locus so identified must be named
according to standard procedures for the species involved.
The allele of the locus identified by the insertion can
then be identified by the abbreviated transgene symbol
according to the conventions adopted for communication,
and supplies a unique identifier to distinguish it from all
other insertions. Each insertion retains the same symbol
even if it is placed on a different genetic background.
Specific lines of animals carrying the insertion should be
additionally distinguished by a stock designator preceding
the transgene symbol. In general, this designator will
follow the established conventions for the naming of
strains or stocks of the particular animal used. In cases
where the background is a mixture of several strains,
stocks, or both, the transgene symbol should be used
without a strain or stock name. For rules on how to
designate strains derived from such mixed genetic
backgrounds or congenic strains or see the section below
on targeted mutations and Sections 3.1.2 and 3.3.
Examples of transgenic strain designations
· C57BL=6J-TgN(CD8GEN)23Jwg The human CD8
genomic clone inserted into C57BL=6 mice from The
Jackson Laboratory (J). The 23rd mouse screened in a
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series of microinjections done in the laboratory of Jon W.
Gordon (Jwg).
· Crl:ICR-TgN(SVDhfr)432Jwg The SV40 early pro-
motor driving a mouse dihydrofolate reductase (Dhfr)
gene. This was a 4 kb plasmid, and this animal was the
32nd animal screened in the laboratory of Jon W. Gordon
(Jwg). The ICR outbred mice were obtained from Charles
River Laboratories (Crl).
· TgN(GPDHim)1Bir The human glycerol phosphate
dehydrogenase, which caused an induced mutation (im);
the first transgenic line produced by Birkenmeier.
Examples of insertional mutation designations
· hoTgN447Jwg The insertion of a transgene into the
hotfoot locus (ho).
· xxx TgN21Jwg The insertion of a transgene that leads to
a recessive mutation in a previously unidentified gene. A
gene symbol for xxx must be obtained from MGD.
Targeted mutations
Rules for symbolizing targeted mutations are given in
Section 1.1.7.7 below. Currently, targeted mutations are
often maintained on a mixed genetic background derived
from the embryonic stem (ES) cell line and the host strain
used. Standardized nomenclature for naming such strains
or for congenic strains made by backcrossing the targeted
mutation onto a standard inbred background is given in
Sections 3.1.2 and 3.3.
1.1.7. Alleles
Alleles are usually designated by the locus symbol with an
added superscript (in italics when printed). In computer-
ized symbols the superscript may be denoted by prefixing
an asterisk or enclosing the allele symbol in angle
brackets, e.g. Gpi1a or Gpi1 a or Gpi1 , a .. For D
symbol locus alleles see section 1.1.3. When a sponta-
neous mutation is cloned or shown to occur in a
previously named candidate gene, the mutation's symbol
is changed to become an allele at the cloned locus by
turning the mutation symbol into an allele symbol, e.g. the
shi (shiverer) mutation in the Mbp (myelin basic protein)
gene becomes Mbpshi . If the original mutation symbol
already has a superscript, the mutation and allele symbols
are placed on one line in the new superscript and
hyphenated, e.g. the shimld (myelin deficient) mutation
becomes Mbpshi-mld (see also #2 below).
1. In the case of mutant genes for which there is
clearly a wild-type, the symbol for the first discovered
mutant allele becomes both the gene symbol and the
symbol for that allele. No superscript is then used, e.g.
Ca, caracul. When a new allele is discovered, it is
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symbolized by adding a superscript to the original
symbol.
2. Recessive alleles should be indicated by the use of
a lower case initial letter for a mutant gene, e.g. a, non-
agouti. All other alleles, whether dominant, codominant
or having dominance relationships that vary with method
of assessment, should be indicated by the use of a capital
initial letter followed by lower case letters, as in the locus
symbol, e.g. Ta, tabby.
Two exceptions to this rule are allowed for targeted
and cloned mutant genes when the original cloned gene
symbol starts with an upper case letter:
1. If the phenotype of mutant alleles may be recessive
or codominant depending on the method of determina-
tion, the use of upper or lower case will depend upon
what the naming investigator considers the defining
phenotype. For example, a targeted mutant allele of Tcra
created by Mombaerts can be symbolized Tcratm1Mom,
even though heterozygotes are not visibly different from
wild-type mice, if heterozygotes can be distinguished at
the DNA or protein level.
2. When a mutation is shown to occur in a cloned
candidate gene and its symbol is changed to become an
allele of the cloned gene (see first paragraph of 1.1.7
above), the first letter of the gene symbol may remain
uppercase and the inheritance pattern may be conveyed in
the allele symbol, e.g. the e (recessive yellow) and Eso
(somber) alleles at the Mc1r (melanocortin 1 receptor)
gene become Mc1r e and Mc1r E-so .
3. Allele superscripts should typically be one or two
lower case letters and, if possible, should convey addi-
tional information about the allele, e.g. pun , pink-eyed
unstable allele of p of pink-eyed dilution. If information
is too complex to be conveyed conveniently in the
symbol, the alleles are given single letter superscripts
and the information concerning the allelic properties is
shown in catalogs or tables, e.g. Pgm1a , Pgm1b ; H2a ,
H2b , etc.
4. For alleles where the allele designates presence or
absence of a virus or immune response, the allele for the
presence of the virus or immune response is designated
by a superscript `a' and the allele for absence of the trait
by a superscript `b'. For loci governing resistance and
susceptibility to infectious organisms or other agents,
resistance is designated by a superscript `r' and
susceptibility by a superscript `s'.
5. Wild-type should be designated by a ‡ sign, with
the locus symbol as superscript, e.g. ‡ p . Reversions from
a mutant allele to wild-type should be distinguished from
the original wild-type allele by designating them by the
locus symbol, with a ‡ sign as superscript e.g. pun‡J .
A ‡ sign alone may be used when the context leaves no
doubt as to the locus represented, e.g. in genetic
formulae.
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6. Indistinguishable alleles of independent origin (e.g.
reoccurrences, reversions to wild-type) should be desig-
nated by the existing gene symbol with a series symbol
(see below) appended as a superscript in italics. If the
gene symbol already has a superscript, this should be
separated from the series symbol by a hyphen. The series
symbol should consist of an arabic numeral correspond-
ing to the serial number of the variant in any given
laboratory, plus the laboratory registration code. To avoid
the confusion of the numberal 1 and the letter l, a first-
discovered variant may be left unnumbered, and the
second variant numbered 2. When two named mutant
genes are found to be alleles at the same locus, the
symbol published or assigned first remains the locus
symbol and the symbol of the second gene is super-
scripted as an allele symbol for that mutation, e.g. hr rh ,
the rhino allele at hairless.
7. Mutations or other variations occurring in known
alleles may be denoted by a superscript m followed by an
appropriate series symbol (as above) and separated from
the original allele symbol, if one exists, by a hyphen, e.g.
Mod1a-m1Lws , the first mutant allele of Mod1a found by
Lewis. For known deletions of all or part of an allele, the
superscript m may be replaced with dl. Information on
the allele of origin of mutations may be valuable in
elucidating changes in DNA sequence. Mutant alleles
created by targeted mutagenesis should have a t
preceding the m to denote targeted, e.g. Cftr tm1Unc , a
targeted mutation of the cystic fibrosis transmembrane
regulator gene created at the University of North
Carolina.
8. Mutant alleles that turn out subsequently to be
deletions retain their allelic designation, e.g. Ta25H and
the various c-locus deletions retain their original symbols
even though they are now known to be deletions that
encompass more than the Ta or c loci. If the deletion
deletes more than one gene and is cytologically visible,
the deletion should be given a chromosome anomaly
designation containing the original allele designation and
the allele symbol is used as the abbreviation. For
example, Del(10)Sl12 1H is the first deletion discovered
at Harwell; it is located on Chromosome 10 and was
originally detected as the 12th steel allele at Harwell
(Sl12H ). Once referred to in a publication by the full
designation, it may be abbreviated Sl12H . Information on
the genes deleted becomes part of the description. If the
deletion deletes more than one gene, but is not
cytologically detectable, the above nomenclature is
discouraged, although a cytological designation may be
given in the future if improved techniques reveal the
deletion cytologically. The term `cytological' refers to
cases where the deletion can be detected by simple
staining methods and visual examination of chromo-
somes. For a deletion of multiple genes detected only by
methods such as in situ hybridization of gene-specific
Rules and guidelines for genetic nomenclature in mice: excerpted version
probes, it is left to the investigator to determine the most
useful terminology.
9. To display polymorphic data from a multipoint
cross in a table for publications, it is acceptable to use
single letter abbreviations for the strains involved in the
cross to designate the strain origin of the alleles. A
footnote to the table should point out that these designate
strain of origin rather than allele symbols, e.g. B for
C57BL=6 vs S for Mus spretus. In databases where
single letters are needed to make comparisons among
strains, the letter used will refer to the `haplotype' or
constellation of different variants revealed by different
assays that make up the phenotype of a particular locus
for a particular strain. The first strain in which the
`phenotype' is described is the prototype and determines
the allele symbol. If two strains thought to have the same
allele are distinguished from each other by a different
assay, one of them is given a new simple allele
designation. Other strains with the original allele
designation, retain the original until they are typed with
the new assay to determine their appropriate allele
designation.
1.1.8. Lethals
Appropriate locus symbols for recessive lethals with no
known heterozygous effect and unidentified function
consist of a lower case letter l followed by the number
of the chromosome on which the locus is located in
parentheses, and series symbol indicating the serial
number of the lethal in the laboratory of origin, e.g.
l(17)2Pas, the second lethal on Chr. 17 found at the
Institut Pasteur.
1.1.9. Viruses
Nomenclature for genes related to the expression of viral
antigens, or to sensitivity or resistance to viruses, should
follow the standard rules for gene nomenclature. Where
possible and appropriate, the letters of the symbol should
be those by which the virus is usually known; e.g. Mtv1, a
locus concerned in induction of mammary tumour virus,
MTV. Successive loci concerned with the same virus
should be distinguished by appending serial numbers; e.g.
Fv1, Fv2.
1.1.10. Oncogenes
Nomenclature for mouse cellular oncogene sequences
should follow the standard nomenclature for oncogenes.
When referring specifically to the mouse locus, however,
in lists of symbols and maps, the prefix c-denoting
cellular sequence should be omitted and the initial letter
of the symbol should be capitalized; e.g. c-myc becomes
Myc. The names and symbols of oncogenes should be
315
regarded as provisional until the true functions of the
genes become known, when they should be renamed, e.g.
Erbb became epidermal growth factor receptor, Egfr.
1.1.11. Phenotype symbols
Phenotype symbols, where these are necessary (e.g.
antigen loci, enzyme loci), should be the same as
genotype symbols except that symbols for phenotypes
should be in capitals, not italicized, and with superscripts
lowered to the line. The phenotypes of heterozygotes
should be written as in the following example: GPI1A,
GPI1B, and GPI1AB are phenotypes associated with the
Gpi1 locus a and b alleles.
1.1.12. Gene complexes
Gene complexes are considered to exist when a number of
apparently functionally or evolutionarily related loci are
genetically closely linked. Alternative states of complexes
are referred to as haplotypes rather than alleles. Known
complexes are of two main types: (a) less extensive
complexes involving duplicate loci or in which operators
or cis-acting regulators of structural genes for protein
show little or no recombination with the loci on which
they act: and (b) very extensive complexes, possibly
involving hundreds of related loci, for which special rules
may be necessary. The H2 and the immunoglobin
complexes are in category (b). The complete nomenclature
rules contain guidelines for less extensive complexes
involving operators, cis-acting regulators, or duplicate
loci, and for very extensive complexes with special rules,
including the H2 complex (see 1.2.3), immunoglobulin
complexes (see 1.2.5), globin gene complexes (see 1.2.4),
homeobox-containing gene complexes (see 1.2.6), and the
t-complex.
1.1.13. Mitochondrial genome
Loci in the mitochondrial genome should be denoted by
the prefix mt-set off from the main symbol by a hyphen.
1.1.14. Antigenic variants
Symbols adopted for loci concerned in cell-mem-
brane alloantigens should be based on the method of
demonstrating such loci. Brief examples of the different
types are listed below with reference to the sections in
which detailed rules, if they exist, can be found.
1. Loci primarily demonstrable by transplantation
techniques should be designated by an initial H; e.g.
H1, H2, etc. (see 1.2.3).
2. Loci demonstrable by red-cell agglutination should
be designated by the letters Ea; e.g. Ea1, Ea2.
316
3. Loci coding for a cell surface molecule on
lymphocytes, or shared by lymphocytes and other cell
types, and detected by serological or biochemical meth-
ods, and for which there is a demonstrable polymorph-
ism, should be designated by the letters Cd, if the CD
antigen is known, and Ly, if not.
4. Similarly, other antigen loci involving other cell
types should be denoted by symbols indicating the cell
type, e.g. Pca, plasma cell antigen; Tla, thymus leuk-
aemia antigen.
The complete text of the nomenclature guidelines
(http://www.informatics.jax.org: Committee, 1996) also
contains detailed rules for naming and symbolizing
pseudogenes, related sequence loci, loci which are
members of a series or family, special gene complexes,
chromosome anomalies and banding patterns, and various
types of mouse strains.
Laboratory Registration Codes
Laboratory Registration Codes originated as a means of
identifying substrains of mice, rats and rabbits held in
different institutions or by different investigators. They
have subsequently come to be used in symbols for
transgenes, DNA loci, targeted mutations, and chromo-
some anomalies. Codes are typically a three-letter
acronym for an institution or an investigator. Only the
first letter of the laboratory code is capitalized. Unique
codes are assigned from a central registry maintained by
the Institute of Laboratory Animal Resources (ILAR) in
Washington, DC, USA. For a current list of approved lab
codes or to register a new lab code, use the World Wide
Web and go to URL address http://www2.nas.edu=
labcode=.
3. Rules for nomenclature for inbred strains and
outbred stocks
3.1.2. Symbols for inbred strains
Inbred strains shall be designated by a capital letter or
letters in roman type or, less preferably, by a combination
of capital letters and numbers, beginning with a letter.
Anyone naming a new strain should consult the most
recent listing of inbred strains (published annually in
Mouse Genome) to avoid duplication. Brief symbols are
preferred. New inbred strain symbols should be registered
as soon as possible after inbreeding is completed. In some
cases an appropriate designation may be reserved prior to
the completion of inbreeding. The contact person for
strain registration is given in current issues of Mouse
Genome.
Exception to the symbol guidelines are allowed in the
case of stocks already widely used and known by
Davisson
designations that do not conform. For example, see
Section 3.1.6. Any strains with a common origin
separated before F20 shall be regarded as related inbred
strains and be given symbols that indicate relationship,
e.g. NZB, NZC, NZO.
Inbred targeted mutation strains derived from only two
strain (including the ES cell line as one) but not exactly
recombinant inbred strains (see below) may be designated
using abbreviations for the two strains separated by a
comma, e.g. B6, 129-gene symbol.
3.1.8. Use of the Laboratory Registration Code to
designate colony holders
A particular colony is normally indicated by appending a
Laboratory Registration Code to the end of the
strain=substrain symbol preceeded by an `@' sign, e.g.
SJL@J, the colony of strain SJL bred at The Jackson
Laboratory. Note that at present there are no recognized
substrains of SJL. Should another substrain be identified
in the future at a different laboratory, The Jackson
Laboratory colony would then be designated SJL=J@J,
or optionally, it could be designated in this way at any
time in anticipation of the development of such substrains.
Other examples: C3H=He@N, the NIH colony of strain
C3H, substrain He, bred at the NIH; CBA=Ca-se@J, the
Ca substrain of CBA, carrying the se mutation, and bred
at The Jackson Laboratory; C57BL=6J@Arc, the J
substrain of substrain 6 of C57BL bred at Arc. If the
substrain symbol and laboratory code are the same, as in
SJL=J@J, for simplicity the @J may be dropped. In all
cases the laboratory code is the last symbol used, and is
meant to indicate that the environmental conditions and
previous history of this colony are unique. The @ symbol
usually signifies a strain or substrain is held in a different
colony from the original but no genetic differences from
the original substrain have been identified and, therefore,
it is not considered a true substrain.
Note that many breeders maintain different colonies of
the same strain and substrain in different animal rooms,
buildings, or even at different sites, but only have a
single laboratory registration code. It is up to the
individual organization to decide whether it would be
appropriate to have a separate laboratory registration code
for each site. As far as possible, in publications the exact
origin of the animals used should be stated.
One significance of manipulative processes such as
fostering is that they may add or eliminate vertically
transmitted viruses. If the identity of an added or
removed virus is known, or if a virus is added artificially,
this should be indicated by appending a symbol for the
virus, in capital letters, followed by a ‡ or ÿ sign
according to whether it is present or absent, e.g.
C3H=He-MTV ‡ @N, a strain produced by inoculating
Rules and guidelines for genetic nomenclature in mice: excerpted version
purified MTV into young hysterectomy-derived C3H=He
mice bred at the NIH.
Because the strain name can not hope to reflect the
full previous history of a strain, breeders are advised to
keep detailed records of the history of the strain,
including details of any manipulation such as cross
fostering, freeze preservation, hysterectomy re-derivation
etc. in case such information may be relevant to the
interpretation of observed results.
Note that previous rules included symbols for various
manipulative procedures as part of the strain nomenclature
(e.g. e ˆ embryo transfer, f ˆ foster nursing, h ˆ hand
rearing, o ˆ ovary transplant, p ˆ freeze preservation,
fh ˆ fostered on hand-reared). These symbols are now
discontinued except where they form part of a well
recognized strain name (e.g. C3HeB=De, a substrain of
C3H formed by transfer of fertilized ova to strain C57BL).
Laboratory Registration Codes should not be accumu-
lated except when long-term maintenance of the colony
results in the establishment of a new substrain according
to current rules (see Section 3.1.5).
3.2. Recombinant inbred and recombinant congenic
strains
1. Recombinant inbred (RI) strains are formed by
crossing two inbred strains, followed by 20 or more
generations of b 3 s mating (Bailey, 1971). The names of
such strains should consist of an abbreviation of both
parental strain names separated by a capital X (the letter
X) with no intervening spaces, e.g. CXB, a set of
recombinant inbred strains derived from a cross of
BALB=c 3 C57BL. Different RI strains in the same
series should be distinguished by numbers (e.g. BXD2,
BXD3, etc.) except for strains already well known by a
different designation. If the abbreviation of the male
parental strain ends in a number, a hyphen may be used
to separate the series numbers that distinguish strains,
e.g. CXB6-2. Punctuation in strain symbols, however, is
to be avoided.
2. Recombinant congenic strains. Strains formed by
crossing two inbred strains, followed by a few (usually
two) brackcrosses to one of the parental strains (the
`background' strain), with subsequent inbreeding without
selection for specific markers are known as recombinant
congenic (RC) strains (Demant and Hart, 1986). RC
strains should be regarded as fully inbred when the
theoretical coefficient of inbreeding approximates that of
a standard inbred strain. For this purpose, one generation
of backcrossing will be regarded as being equivalent to
two generations of brother 3 sister mating. Thus a strain
produced by two backcrosses (N3, equivalent to F6 )
followed by 14 generations of b 3 s mating (F14 ) would
be fully inbred. RC strains are designated by an upper
case abbreviation of the names of the two parental strains
317
(with the recipient strain given first, followed by the
donor strain) separated by a lower case `c' (e.g. CcS, a
set of recombinant congenic strains from a cross between
BALB=c and STS, backcrossed to BALB=c). Individual
strains of the series are distinguished by appending
numbers to the strain symbols (e.g. CcS1). Avoid
hyphenated symbols unless the second strain ends in a
number. The number of generations of backcrossing
should normally form part of the history of each
individual strain, but may be indicated in parentheses
where more than two backcross generations were used
(e.g. CcS1(N4)).
3.3. Co-isogenic, congenic and segregating inbred
strains
Two strains that are genetically identical (i.e. isogenic),
except for a difference at a single locus, are called co-
isogenic. True co-isogenicity can probably be achieved
only by mutation within an existing inbred strain, while
lines obtained by inbreeding with forced heterozygosis
(segregating inbred), or by backcrossing to an inbred
strain (congenic), usually differ in a short chromosomal
segment rather than a single gene.
1. Co-isogenic strains are formed by the occurrence of
a mutation within an inbred strain. They should be
designated by the strain symbol and, where appropriate,
the substrain symbol followed by a hyphen and the gene
symbol of the differential allele (in italics in printed
articles e.g. DBA=Ha-d‡ ). When the mutant gene is
maintained in the heterozygous condition, this should be
indicated by including a `‡' sign in the symbol: e.g.
A=Faÿ‡=c; C3H=Nÿ‡=W v. Such strains differ from the
substrains described in Section 3.1.5 and 3.1.6 in that in
co-isogenic strains the genetic difference is simple and
precisely defined. The number of generations of inbreed-
ing since the mutation arose in a co-isogenic strain
should be indicated by intercalating a ‡, or ‡ M ‡ in the
indication of inbreeding, e.g. F110 ‡ F23 or F110 ‡
M ‡ F23, 23 generations of b 3 s matings since the
occurrence of a mutation at F110 in an inbred strain.
2. Congenic strains are produced by repeated back-
crosses to an inbred strain. They should be designated by
a compound symbol consisting of two parts separated by
a period: the full or abbreviated symbol of the back-
ground strain followed by (i) a period and an abbreviated
symbol of the donor strain, and (ii) a hyphen and the
symbol of the differential locus or loci and allele(s) (in
italics), e.g. B10.129- H-12b , a strain with the genetic
background of C57BL=10Sn (ˆB10), but which differs
from that strain in a differential allele ( H-12b ) derived
from strain 129=J. If several lines derived from the same
donor strain are available, the individual lines are
distinguished by a number and=or letter in parentheses;
318
e.g. B10.129(12M)- H-12 b , B10.129(21M)- H-4 b p. In
cases where the use of such a full symbol is
inappropriate, as when the donor strain is not inbred, or
the genetic difference is complex, or where the strain is
already widely known, a less complete symbol may be
used, e.g. B10- pa H-3e at ; B10.129(5M); A.SW.
Congenic lines that differ at a histocompatibility locus
and, therefore, resist each other's grafts are called
congenic resistant (CR) lines.
A strain developed by this method shall be regarded as
congenic when a minimum of 10 backcross generations to
the background strain have been made, counting the first
hybrid or F1 generation as generation 1. The number of
backcross generations shall be indicated by N and the
number in parentheses. In the case where it is necessary to
employ more complex mating systems, the generations
should be expressed as N equivalents (NE) and the strain
regarded as congenic at a minimum of NE10. For
example, when backcrossing a recessive gene onto an
inbred background, after 10 rounds of backcrossing and
intercrossing (to recover a homozygote for the next
backcross), the strain would be at NE10. When a congenic
strain is maintained by b 3 s matings after backcrossing,
the number of b 3 s generations follows the number of
backcross generations, e.g. (N10F6), 10 generations of
backcrossing followed by 6 generations of b 3 s inbreed-
ing; (NE12F17), a complex system of backcrosses and
intercrosses genetically equivalent to 12 backcrosses,
followed by 17 generations of b 3 s matings.
3. Segregating inbred strains are developed by in-
breeding with forced heterozygosis. They shall be
designated, like co-isogenic strains, by a strain symbol
followed by a hyphen and the gene symbol of the
segregating locus. Indication of the segregating locus is
optional when it is part of the standard genotype of that
strain, and the hyphen or entire gene symbol may be
omitted; examples are 129 or 129 cch= c (129 is
customary); WBÿW=‡ or WB. The minimal inbreeding
requirement for such a strain shall be the same as that
for an inbred strain, i.e. 20 generations of b 3 s matings.
For segregating inbred strains developed by inbreeding
with forced heterozygosis, the number of generations of
such breeding may be indicated by FH and the number in
parentheses, e.g. (FH27), a strain developed by 27
generations of b 3 s matings with forced heterozygosis.
4. Consomic strains are produced by repeated back-
crossing of a whole chromosome such as the X or Y
chromosome onto an inbred strain. The generic designa-
tion for consomic strains is HOST STRAIN-
CHROMOSOME DONOR STRAIN , e.g. C57BL=6J-YAKR is a
consomic strain with the Y-chromosome of strain AKR
backcrossed onto C57BL=6J. When the chromosome
comes from a non-inbred background, an appropriate
abbreviation designating the stock or origin may be used,
e.g. C57BL=6J-YDOM has a M.m. domesticus Y-chromo-
Davisson
some backcrossed to C57BL=6J. In these cases, no period
followed by the donor strain is required because the
strain of origin is shown in the superscript. Capitalization
of all letters in the superscript distinguishes it from allele
symbols which are lower case. As with congenic strains,
a minimum of 10 backcross generations is required,
counting the F1 generation as gernation 1.
5. Conplastic strains are developed by backcrossing the
nuclear genome from one strain into the cytoplasm of
another, i.e. the mitochondrial parent is always the female
parent during the backcrossing program. The designation
is NUCLEAR GENOME-mtCYTOPLASMIC GENOME , e.g.
C57BL=6J-mtBALB=c , is a strain with the nuclear genome
of C57BL=6J, and the cytoplasmic genome of BALB=c,
developed by crossing male C57BL=6J mice with
BALB=c females, followed by repeated backcrossing of
female offspring to male C57BL=6J. As with congenic
strains, a minimum of 10 backcross generations is
required, counting the F1 generation as generation 1.
3.4. Hybrids
F1 hybrids are designated by listing the female progenitor
first and the male progenitor second. The symbol can be
abbreviated using standard strain abbreviations. Thus,
B6D2F1 mice are the offspring of a C57BL=6J female
mated to a DBA=2J male; D2B6F1 mice are offspring of
the reciprocal mating. The two F1 hybrids differ in the Y-
chromosome present in the males, and have been exposed
to a different maternal environment. They should not be
considered genetically identical. The correct full strain
symbol should be given the first time the hybrid is
mentioned in a publication; the abbreviated symbol can be
used subsequently. Hybrids from backcrosses and three- or
four-way crosses can be designated in the same way, that
is, by giving the designation of the female parent first and
the designation of the male parent second. The hybrid
parent in such a cross is enclosed in parentheses followed
by the generation number, e.g. B6(D2AKRF1). The
construction of these hybrids should be described in full
with complete strain designations before using the
abbreviated symbol.
3.5. Laboratory mice and outbred stocks
In addition, to standard inbred strains, there is a need for
standard ways to refer to laboratory mice in general and to
outbred stocks.
1. Laboratory mice. Since laboratory strains are
neither pure Mus domesticus nor Mus musculus, they
should be referred to with the words `laboratory mice' or
by the inbred strain name when known.
2. Non-inbred stocks. Outbred or random bred stocks
are sometimes given specific designations if they meet
Rules and guidelines for genetic nomenclature in mice: excerpted version
specific criteria (ICLA, 1972). Stock designations must
not be the same as those for inbred strains of the same
species. New stock symbols should be registered as for
inbred strains (see 3.1.2 and 3.1.7).
Summary
The rules and guidelines for genetic nomenclature in mice
are intended to ensure the accurate and unique identifica-
tion of genes, genetically manipulated mice and strains.
The Nomenclature Committee strongly urges the scientific
community to follow the rules as closely as possible. The
rapid advances in genetic technology and molecular
characterization of genes, however, are continually pre-
senting the Committee with situations that the rules do not
quite fit. Thus, the guidelines are intended to provide
guidance for naming and symbolizing genetic elements
without being absolutely rigid. For example, despite
several attempts over the past 15 years to develop a
standard nomenclature for trangenes, nomenclature used
by investigators still is not consistent across transgenic
methods and models. Most recently, a committee formed
by the Institute of Laboratory Animal Resources drew up
guidelines, soliciting input from many members of the
scientific community who were currently making trans-
genic animals (ILAR, 1992). The nomenclature proposed
by this committee was an attempt to strike a balance
between the long and, often complicated, symbols some
investigators wanted to use and the simple three-four letter
symbols others favoured. Once a complete symbol is used
in a paper and a shorter, more common abbreviation is
introduced, the abbreviation can be use throughout the rest
of the paper. The most important principle to keep in mind
when symbolizing genes, transgenes, targeted mutations,
or strains and stocks is that the purpose of the symbol is
to provide a unique identifier or name and not to convey
all the information known about the genetic element being
symbolized. When in doubt about a symbol, we encourage
you to contact a member of the Nomenclature Committee
(see MGD, http://www.informatics.jax.org) or the MGD,
nomenclature coordinator.
References
Bailey, D.W. (1971) Recombinant inbred strains, an aid to finding
identity, linkage, and function of histocompatibility and other
genes. Transplantation 11, 325±7.
Committee on Standardized Genetic Nomenclature for Mice
(1996a) Rules and guidelines for gene nomenclature. In:
319
Lyon, M.F., Rastan, S. and Searle, A.G. eds. Genetic Variants
and Strains of The Laboratory Mouse, 3rd Ed. Oxford, UK:
Oxford University Press, pp. 1±16.
Committee on Standarized Genetic Nomenclature for Mice (1996b)
Rules for nomenclature of chromosome anomalies. In: Lyon,
M.F., Raston, S. and Searle, A.G. eds. Genetic Variants and
Strains of The Laboratory Mouse, 3rd Ed. Oxford; UK:
Oxford University Press. pp. 1443±5.
Committee on Standardized Genetic Nomenclature for Mice
(1996c) Rules for nomenclature of inbred strains. In: Lyon,
M.F., Raston, S. and Searle, A.G. Genetic Variants and Strains
of the Laboratory Mouse, 3rd Ed. Oxford, UK: Oxford
University Press. pp. 1532±6.
Demant, P. and Hart, A.A.M. (1986) Recombinant congenic strains
± a new tool for analyzing genetic traits determined by more
than one gene. Immunogenetics 24, 416±22.
ICLA (International Committee on Laboratory Animals) (1972)
International standardized nomenclature for outbred stocks of
laboratory animals. ICLA Bull. 30, 4±17.
ILAR (Institute of Laboratory Animal Resources), Committee on
Transgenic Nomenclature (1992) Standardized nomenclature
for transgenic animals. ILAR News, 34, 45±52.
MGD (Mouse Genome Database), Mouse Genome Informatics,
The Jackson Laboratory, Bar Harbor, Maine. World Wide Web
(URL: http://www.informatics.jax.org=).
Additional Bibliography
Beechey, C.V. (1992) Maps of chromosome anomalies in the
mouse. Mouse Genome 90, 45±65.
Evans, E.P. (1989) Standard normal chromosomes In: Lyon, M.F.,
Rastan, S. and Searle, A.G. eds. Genetic Variants and Strains
of the Laboratory Mouse, 3rd ed., Oxford, UK: Oxford
University Press, pp. 1446±1451.
IUPAC-IUB Commission on Biochemical Nomenclature (CBN)
(1978) Nomenclature of multiple forms of enzymes. Recom-
mendations (1976). Arch. Biochem. Biophys. 185, 1±3.
Klein, J. and others (1990) Revised nomenclature of mouse H-2
genes. Immunogenetics 32, 147±149.
Lyon, M.F., Barker, J.E. and Popp, R.A. (1988) Mouse globin gene
nomenclature. J. Hered. 79, 93±5.
Morse, H.C. (1992) Genetic nomenclature for loci controlling
surface antigens of mouse hemopoietic cells. J. Immunol. 149,
3129±34.
Nesbitt, M.N. and Francke, U. (1973) A system of nomenclature
for band patterns of mouse chromosomes. Chromosoma 41,
145±58.
Sawyer, J.R., Moore, M.M. and Hozier, J.C. (1987) High resolution
G-banded chromosomes of the mouse. Chromosoma 95,
350±8.
Scott, M.P. (1992) Vertebrate homeobox gene nomenclature. Cell
71, 551±3.