References
Query Results -- Details
MGI Accession ID: MGI:3844790
J Number: J:148437
Other Accession IDs:
Title: Rac GTPases play critical roles in early T-cell development.
Authors: Dumont C; Corsoni-Tadrzak A; Ruf S; de Boer J; Williams A; Turner M; Kioussis D; Tybulewicz VL
Journal: Blood
Volume: 113
Issue: 17
Date: 2009 Apr 23
Year: 2009
Pages: 3990-8
Review Status: Peer Reviewed
Abstract:
The Rac1 and Rac2 GTPases play important roles in many processes including cytoskeletal reorganization, proliferation, and survival, and are required for B-cell development. Previous studies had shown that deficiency in Rac2 did not affect T-cell development, whereas the function of Rac1 in this process has not been investigated. We now show that simultaneous absence of both GTPases resulted in a very strong developmental block at the pre-TCR checkpoint and in defective positive selection. Unexpectedly, deficiency of Rac1 and Rac2 also resulted in the aberrant survival of thymocytes lacking expression of TCR beta, showing hallmarks of hyperactive Notch signaling. Furthermore, we found a similar novel phenotype in the absence of Vav1, Vav2, and Vav3, which function as guanine nucleotide exchange factors for Rac1 and Rac2. These results show that a pathway containing Vav and Rac proteins may negatively regulate Notch signaling during early thymic development.
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