International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

Table of Contents * Genes, Physical Mapping and Sequencing * Gene Identification * Bioinformatics * Common Resources * RIKEN Session * Functional Genomics * Complex Traits * Mutagenesis * Developmental Genetics and Differentiation * Verne Chapman Memorial Lecture I and II

H18. Mutant Mice Lacking Crk-II Caused by Gene Trap Insertional Mutagenesis: Crk-II Is Not Essential for Embryonic Development

Tomohisa Sekimoto^1,4, Takashi Imaizumi¹, Katsutaka Miura¹, Masatake Araki², Misao Suzuki³, Naoya Tajima⁴, Kimi Araki¹, Ken-ichi Yamamura^1,3
1 Dept. of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, ²Gene Technology Center, ³Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan. ⁴Dept. of Orthopaedics Surgery, Miyazaki Medical College, Miyazaki, Japan.

Crk family adapter proteins including Crk-II, Crk-I and Crk-L consist mostly of SH2 and SH3 domains. Through the interactions between the SH2 domain and phosphotyrosine residues and/or between the SH3 domain and proline-rich motifs, they are involved in a variety of signaling cascades. Despite their essential roles in signal transduction, knock-out mice as to these molecules have not been reported yet. We performed gene trap insertional mutagenesis with a trap vector, pU-Hachi, and generated a mutant mice line, Ayu 8104, in which the trap vector is inserted into the c-crk gene. Homozygous Ayu 8104 mice lacked Crk-II and Crk-I transcripts but expressed truncated Crk proteins retaining one SH2 and one SH3 domain. Since the structures of the truncated proteins were similar to that of Crk-I, the insertion was considered to cause Crk-II specific disruption. Homozygous mutant mice, however, did not exhibit any obvious abnormalities, suggesting that Crk-family adapters, Crk-II, Crk-I and Crk-L would redundantly function in the signaling cascades and that Crk-II is not apparently essential for embryonic development.