International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 59 - GENETIC AND BIOCHEMICAL CHARACTERIZATION OF AN ALLELIC SERIES OF SMAD4 MUTATIONS IDENTIFIED IN AN ENU-MUTAGENIZED MOUSE EMBRYONIC STEM CELL LIBRARY

Chen Y, Yee D, Magnuson T

University of North Carolina-Chapel Hill, Chapel Hill, United States

Genotyped-based screens in mutagenized mouse embryonic stem cells represent a rapid and cost-effective means of generating germline mutations valuable for the functional annotation of the mammalian genome.  Smad4 is central to the TGF--related signaling and is implicated in numerous developmental and disease processes.  Targeted mutations in Smad4 cause early lethality, making the study of its later functions difficult.  An allelic series of mutations in Smad4 was obtained by screening a cryopreserved ES cell library mutagenized with ENU using the DHPLC mutation detection technology.  The identified mutations were distributed throughout the coding region of the Smad4 gene.  The functional consequence of the mutations is assessed through germline transmission.  The phenotypes range from embryonic lethality to adult viability.  The genetic and biochemical characterization of this allelic series of mutations in Smad4 provides insights into the in vivo relationship of structure and function of this family of molecules. 

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