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- Title
A Genetic Screen for Modifiers of the Deltal-Dependent Notch Signaling Function in the Mouse.
- Authors
Rubio-Aliaga, Isabel; Soewarto, Dian; Wagner, Sibylle; Klaften, Matthias; Fuchs, Helmut; Kalaydjiev, Svetoslav; Busch, Dirk H.; Klempt, Martina; Rathkolb, Birgit; Wolf, Eckhard; Abe, Koichiro; Zeiser, Stefan; Przemeck, Gerhard K. H.; Beckers, Johannes; de Angelis, Martin Hrabé
- Abstract
The Notch signaling pathway is an evolutionarily conserved transduction pathway involved in embryonic patterning and regulation of cell fates during development. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, which are also involved in distinct human diseases. Delta1 is one of the known ligands of tile Notch receptors. Mice homozygous for a loss-of-function allele of the Deltal gene Dll1IncZ/IncZ die during embryonic development. Here, we present the results of two phenotype-driven modifier screens. Heterozygous Dll1IncZ knockout animals were crossed with ENU-mutagenized mice and screened for dysmorphological, clinical chemical, and immunological variants that are dependent on the Delta1 loss-of-function allele. First, we show that mutagenized heterozygous Dll1IncZ offspring have reduced body weight and altered specific clinical chemical parameters, including changes in metabolites and electrolytes relevant for kidney function. In our mutagenesis screen we have successfully generated 35 new mutant lines. Of major interest are 7 mutant lines that exhibit a Dll1IncZ/+-dependent phenotype. These mutant mouse lines provide excellent in vivo tools for studying the role of Notch signaling in kidney and liver function, cholesterol and iron metabolism, cell-fate decisions, and during maturation of T cells in the immune system.
- Subjects
GENETIC testing; NOTCH genes; IMMUNE system; METABOLITES; ELECTROLYTES; LABORATORY mice; ANIMAL models in research; GENETIC research
- Publication
Genetics, 2007, Vol 175, Issue 3, p1451
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1534/genetics.106.067298