Mutant mice lacking Crk-II caused by the gene trap insertional mutagenesis : Crk-II is not essential for embryonic development

Crk family adapter proteins including Crk-II, Crk-I, and Crk-L consist mostly of SH2 and SH3 domains. Through the interactions between SH2 domain and phosphotyrosine residues and/or between SH3 domain and proline-rich motifs, they are involved in a variety of signaling cascades. Despite their essential roles in the signal transductions, knock-out mice of these molecules have not been reported yet. We performed the gene trap insertional mutagenesis with a trap vector, pU-Hachi, and generated a mutant mice line, Ayu 8104, in which the trap vector was inserted into the c-crk gene. Homozygous Ayu 8104 mice lacked Crk-II and Crk-I transcripts but expressed the truncated Crk proteins retaining one SH2 and one SH3 domain. Since the structure of the truncated proteins was 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 Crk-II was not apparently essential for embryonic development.