The Xenopus embryo's amenability to functional assays has made it one of the most productive model systems for biomedical research in the molecular era. Its high degree of conserved gene structure and function means that results from Xenopus can usually be applied to other vertebrates, such as human and mouse, while its experimental manipulability and unparalleled embryology allow rapid and direct characterization of gene activities. The worldwide Xenopus research community is large and growing, with increasing adoption of Xenopus tropicalis for conventional Ioss-of-function genetic experiments and other genomic approaches. Xenopus research has recently begun to be transformed by the application of reverse genetics, driven by the availability of sequence from a variety of EST and full-length cloning projects as well as the recent whole-genome shotgun sequence for Xenopus tropicalis. Over the next five years, using a well-established reverse genetic strategy, we will identify carriers of chemically-induced Xenopus tropicalis mutations in known genes at a rate of 35 loci per year, generating an international resource of null as well as hypomorphic alleles. In addition, for each gene we will provide a first-pass phenotypic analysis of predicted null alleles, including morphological screening, a standard set of in situ hybridisations, and transcriptional profiling using a small cDNA microarray. The establishment of this major resource will generate a high degree of synergy within the community, allowing the field to combine the full breadth of Xenopus functional approaches with previously unavailable defined genetic deficiencies, greatly contributing to our understanding of gene function in vertebrate development and disease. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD054354-02
Application #
7408033
Study Section
Special Emphasis Panel (ZRG1-GGG-T (52))
Program Officer
Coulombe, James N
Project Start
2007-04-20
Project End
2012-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
2
Fiscal Year
2008
Total Cost
$395,227
Indirect Cost
Name
Sanger Institute
Department
Type
DUNS #
346013253
City
Cambridge
State
Country
United Kingdom
Zip Code
Abu-Daya, Anita; Khokha, Mustafa K; Zimmerman, Lyle B (2012) The hitchhiker's guide to Xenopus genetics. Genesis 50:164-75
Showell, Chris; Carruthers, Samantha; Hall, Amanda et al. (2011) A comparative survey of the frequency and distribution of polymorphism in the genome of Xenopus tropicalis. PLoS One 6:e22392
Young, John J; Cherone, Jennifer M; Doyon, Yannick et al. (2011) Efficient targeted gene disruption in the soma and germ line of the frog Xenopus tropicalis using engineered zinc-finger nucleases. Proc Natl Acad Sci U S A 108:7052-7