Xenbase

Xenbase is a Model Organism Database

(MOD), providing informatics resources, as
well as genomic and biological data on
Xenopus frogs.[1] Xenbase has been
available since 1999, and covers both X.
laevis and X. tropicalis Xenopus varieties.[2]
As of 2013 all of its services are running on
virtual machines in a private cloud
environment, making it one of the first
MODs to do so.[3] Other than hosting
genomics data and tools, Xenbase supports
the Xenopus research community though
profiles for researchers and laboratories, and
job and events postings.
Xenbase's Software and
Hardware Platform
Xenbase runs in a cloud environment.[3] Its
virtual machines are running in a VMware
vSphere environment on two servers, with
automatic load balancing and fault
tolerance. Xenbase software uses Java, JSP,
JavaScript, AJAX, XML, and CSS. It also
uses Apache Tomcat and the IBM DB2
database. The same hardware and software
platforms support Echinobase.
Xenbase
Content
Description Xenbase: The Xenopus Model
Organism Knowledgebase.
Data types Phenotypes, Diseases, Literature,
captured Nucleotide Sequence, RNA sequence,
Protein sequence, Structure,
Genomics, Morpholinos, Metabolic and
Signaling Pathways, Human and other
Vertebrate Genomes, Human Genes
and Diseases, Microarray Data and
other Gene Expression, Proteomics
Resources, Other Molecular Biology,
Organelle
Organisms Xenopus laevis and Xenopus tropicalis
Contact
Research center Cincinnati Children's Hospital,
University of Calgary
Laboratory Zorn lab (http://www.cincinnatichildren
s.org/research/divisions/d/dev-biology/l
abs/zorn/default/), Vize lab (http://www.
vizelab.com/)

Supported Species Primary citation PMID 29059324 (https://pubmed.ncbi.n

lm.nih.gov/29059324)
Xenbase offers two levels of support. Full Release date 1999
support includes full genome integration in Access
the database, including gene pages,
BLAST, JBrowse, and genome downloads. Website https://www.xenbase.org/
Partial support provides BLAST, JBrowse, Download URL https://download.xenbase.org/xenbase/
and download options, but no gene page Tools
integration.
Standalone BLAST, JBrowse
Full support: Xenbase's primary mission is Miscellaneous
to provide comprehensive support for the
following frogs License Public domain
Data release Continuous
Xenopus laevis (Africal clawed frog) frequency
 Xenopus tropicalis (Western clawed Version 6.x
frog)
Curation policy Professionally curated
Partial support: Bookmarkable Yes
entities
Rana catesbeiana (American
bullfrog)
Nanorana parkeri (High Himalaya frog)
Ambystoma mexicanum (Axolotl)
Hymenochirus boettgeri (Zaire or Congo dwarf clawed frog)

Xenopus as a Model Organism

The Xenopus model organism is responsible for large amounts of new knowledge on embryonic
development and cell biology. Xenopus has a number of unique experimental advantages as a vertebrate
model. Paramount among these is the robustness of early embryos and their amenability to microinjection
and microsurgery. This makes them a particularly attractive system for testing the ectopic activity of gene
products and loss-of-function experiments using antagonizing reagents such as morpholinos, dominant-
negatives and neomorphic proteins. Morpholinos are synthetic oligonucleotides that can be used to inhibit
nuclear RNA splicing or mRNA translation and are the common gene inhibition reagent in Xenopus as
neither siRNA or miRNA have yet been shown to reproducibly function in frog embryos.[4] Xenopus
embryos develop very quickly and form a full set of differentiated tissues within days of fertilization,
allowing rapid analysis of the effects of manipulating embryonic gene expression.[5] The large size of
embryos and amenability to microinjection also makes them extremely well suited to microarray
approaches. Furthermore, these same characteristics make Xenopus, one of the few vertebrate model
organisms suited for chemical screens.[6] Xenbase provides a large database of images illustrating the full
genome, movies detailing embryogenesis, and multiple online tools useful for designing and conducting
experiments using Xenopus.

Xenopus as a Human Disease Model

Xenopus can be used to model human diseases caused by common genes.[7] Xenbase supports this by
mapping Disease Ontology and OMIM diseases to Xenopus genes and publications. Xenopus phenotype
data, as well as links to comparable human and mouse phenotypes and diseases (via the Monarch Initiative)
are also provided.

Xenbase Contents and Tools

Xenbase provides many tools useful for both professional research as well as academic learning.
Highlighted below are a few of the tools, along with a brief description. For full details on provided tools,
users are referred to Xenbase's publications.[8] A detailed introduction to using Xenabse comes in.[9]

Phenotype support,[10] including Monarch Initiative (human and mouse) data links
Diseases - Users can search for both Disease Ontology and OMIM diseases to find relevant
Xenopus genes and publications
NGS RNA-Seq and ChIP-Seq data integration and visualization from Gene Expression
Omnibus (GEO).[11]
RNA-Seq viewers - Graphs of temporal expression profiles and spatial (anatomy)
expression heatmaps for both laevis and tropicalis
 Gene Expression - Xenbase supports search and visualization of Gene Expression
Omnibus (GEO) data sets, mapped to the latest Xenopus genomes.
BLAST - Users can BLAST against Xenopus genomes, RNA, and protein sequences
Genome browser - Xenbase uses both JBrowse and GBrowse
Expression Search and Clone Search - Search by gene symbol, gene name, anatomy
item, etc.
Gene nomenclature guidelines - Xenbase is the official body responsible for Xenopus
gene naming
Literature search: Textpresso- Uses an algorithm to match your search to specific criteria
or section of a paper. For example, you could identify papers describing HOX genes and
limit your results to only papers which used morpholinos.
Anatomy and Development: Images, fate maps, videos, etc.
Community Link - People, jobs, labs which study Xenopus
Protocol List- Identify clones, antibodies, procedures
Stock Center- Supports the National Xenopus Resource, the European Xenopus Resource
Centre, etc. to help researchers with obtaining frog stocks or advanced research training

2012 Nobel Prize in Xenopus Research

The Nobel Prize for Medicine or Physiology was awarded to John B. Gurdon and Shinya Yamanaka on
October 8, 2012.[12] for nuclear reprogramming in Xenopus.[13]

Importance: Gurdon's experiments challenged the dogma of the time which suggested that the nucleus of
a differentiated cell is committed to their fate (Example: a liver cell nucleus remains a liver cell nucleus and
cannot return to an undifferentiated state).

Specifically, John Gurdon's experiments showed that a mature or differentiated cell nucleus can be returned
to its immature undifferentiated form; this is the first instance of cloning of a vertebrate animal.

Experiment: Gurdon used a technique known as nuclear transfer to replace the killed-off nucleus of a frog
(Xenopus) egg with a nucleus from a mature cell (intestinal epithelial). The tadpoles resulting from these
eggs did not survive long (past the gastrulation stage), however, further transformation of the nuclei from
these Xenopus eggs to a second set of Xenopus eggs resulted in fully developed tadpoles. This process
(transfer of nuclei from cloned cells) is referred to as serial transplantation.

Xenopus Research Utilizing Xenbase Tools

To provide examples of how Xenbase could be used to facilitate academic research, two research articles
are briefly described below.

Genetic Screens for Mutations Affecting Development of X. tropicalis.[14]

This paper uses Xenbase resources to create and characterize mutations in Xenopus tropicalis. Goda et al.,
performed a large scale forward genetics screen on X. tropicalis embryos to identify novel mutations
(2006). Defects were noted and put into 10 different categories as follows: eye, ear, neural crest/pigment,
dwarf, axial, gut, cardiovascular, head, cardiovascular plus motility, and circulation. Further studies were
performed on the whitehart mutant "wha" which does not have normal circulating blood. The Xenopus
Molecular Marker Resource page was used to design a microarray experiment which compared wild type
(normal circulation) and "wha" mutant X. tropicalis. Analysis of microarray data revealed that 216 genes
had significant changes in expression, with genes involved in hemoglobin and heme biosynthesis being the
most affected, consistent with the observation that "wha" may have a role in hematopoiesis.

High efficiency TALENs enable F0 functional analysis by targeted gene disruption in

Xenopus laevis embryos.[15]

The 2013 paper by Suzuki et al. describes the use of a relatively new gene knockdown technique in X.
laevis. Traditionally, antisense morpholino oligonucleotides have been the method of choice to study the
effects of transient gene knockdown in Xenopus.

In comparison to morpholinos which disrupt gene expression by inhibiting translational machinery

TALENs disrupt gene expression by binding to DNA and introducing double stranded breaks.[16][17]
Xenbase was utilized to obtain publicly available sequences for tyrosinase (tyr) and Pax6, needed for
TALEN design. Knockdown of both Pax6 and tyr was highly efficient using TALENs, suggesting that
gene disruption using TALENs may be an alternative or better method to use in comparison to antisense
morpholino's.

See also
Echinobase
FlyBase
WormBase
Mouse Genome Informatics
ZFIN
DictyBase

References
1. M. Fisher et al. (2023) Xenbase: key features and resources of the Xenopus model organism
knowledgebase (https://academic.oup.com/genetics/article/224/1/iyad018/7031801),
Genetics, Volume 224, Issue 1, May 2023, iyad018,
2. P.D. Vize et al. (2015) Database and informatic challenges in representing both diploid and
tetraploid Xenopus species in Xenbase (https://www.karger.com/Article/Abstract/430427),
Cytogenet Genome Res 2015;145:278-282
3. K. Karimi and P.D. Vize (2014). The Virtual Xenbase: transitioning an online bioinformatics
resource to a private cloud (https://academic.oup.com/database/article-lookup/doi/10.1093/d
atabase/bau108), Database, doi: 10.1093/database/bau108
4. Eisen, J.a.S., J. . (2008). Controlling morpholino experiments: don't stop making antisense.
Development, 135(10): p. 1735-1743.
5. Gene expression data for Pax8 gene on xenbase's site (http://www.xenbase.org/gene/expre
ssion.do?method=displayGenePageExpression&geneId=483692&geneSymbol=pax8&gen
eName=paired%20box%208&tabId=1)
6. Wheeler, G. N. and A. W. Brändli (2009). "Simple vertebrate models for chemical genetics
and drug discovery screens: Lessons from zebrafish and Xenopus." Developmental
dynamics 238(6): 1287-1308.
7. Nenni et al. (2019). Xenbase: Facilitating the use of Xenopus to Model Human Disease (http
s://www.frontiersin.org/articles/10.3389/fphys.2019.00154/full), Frontiers in Physiology,
Volume 10, doi:10.3389/fphys.2019.00154
8. "Xenbase publications" (http://www.xenbase.org/other/static-xenbase/citingMOD.jsp).
 9. James-Zorn et al. (2018) Navigating Xenbase: An Integrated Xenopus Genomics and Gene
Expression Database (https://link.springer.com/protocol/10.1007/978-1-4939-7737-6_10),
Eukaryotic Genomic Databases: Methods and Protocols, Volume 1757, Chapter 10, pp. 251-
305, doi:10.1007/978-1-4939-7737-6
10. M. Fisher et al. (2022) The Xenopus phenotype ontology: bridging model organism
phenotype data to human health and development (https://link.springer.com/article/10.1186/s
12859-022-04636-8), BMC bioinformatics, 23, 99
11. Fortriede et al. (2020) Xenbase: deep integration of GEO & SRA RNA-seq and ChIP-seq
data in a model organism database (https://academic.oup.com/nar/article/48/D1/D776/56265
30), Nucleic Acids Research (NAR), Volume 48, Issue D1, 08 January 2020, Pages D776–
D782, doi:https://doi.org/10.1093/nar/gkz933
12. "The 2012 Nobel Prize in Physiology or Medicine - Press Release" (https://www.nobelprize.
org/nobel_prizes/medicine/laureates/2012/press.html).
13. Gurdon, J.B. (1962). The Developmental Capacity of Nuclei taken from Intestinal Epithelium
Cells of Feeding Tadpoles. Journal of Embryology and Experimental Morphology, 10(4): p.
622-640
14. Goda, T., Abu-Daya, Anita, Carruthers, Samantha, Clark, Matthew D., Stemple, Derek L.,
Zimmerman, Lyle B. (2006). " Genetic Screens for Mutations Affecting Development of
Xenopus tropicalis." PLoS Genet 2(6): e91
15. Suzuki, K.-i. T., Y. Isoyama, et al. (2013). "High efficiency TALENs enable F0 functional
analysis by targeted gene disruption in Xenopus laevis embryos." Biology Open
16. Boch, J. (2011). "TALEs of genome targeting." Nat Biotech 29(2): 135-136
17. Huang, P., A. Xiao, et al. (2011). "Heritable gene targeting in zebrafish using customized
TALENs." Nat Biotech 29(8): 699-700

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