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Publication : An ENU-mutagenesis screen in the mouse: identification of novel developmental gene functions.

First Author  Wansleeben C Year  2011
Journal  PLoS One Volume  6
Issue  4 Pages  e19357
PubMed ID  21559415 Mgi Jnum  J:173681
Mgi Id  MGI:5049934 Doi  10.1371/journal.pone.0019357
Citation  Wansleeben C, et al. (2011) An ENU-mutagenesis screen in the mouse: identification of novel developmental gene functions. PLoS One 6(4):e19357
abstractText  BACKGROUND: Mutagenesis screens in the mouse have been proven useful for the identification of novel gene functions and generation of interesting mutant alleles. Here we describe a phenotype-based screen for recessive mutations affecting embryonic development. METHODOLOGY/PRINCIPAL FINDINGS: Mice were mutagenized with N-ethyl-N-nitrosourea (ENU) and following incrossing the offspring, embryos were analyzed at embryonic day 10.5. Mutant phenotypes that arose in our screen include cardiac and nuchal edema, neural tube defects, situs inversus of the heart, posterior truncation and the absence of limbs and lungs. We isolated amongst others novel mutant alleles for Dll1, Ptprb, Plexin-B2, Fgf10, Wnt3a, Ncx1, Scrib(Scrib, Scribbled homolog [Drosophila]) and Sec24b. We found both nonsense alleles leading to severe protein truncations and mutants with single-amino acid substitutions that are informative at a molecular level. Novel findings include an ectopic neural tube in our Dll1 mutant and lung defects in the planar cell polarity mutants for Sec24b and Scrib. CONCLUSIONS/SIGNIFICANCE: Using a forward genetics approach, we have generated a number of novel mutant alleles that are linked to disturbed morphogenesis during development.
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