Csk (c-src tyrosine kinase) is a negative regulator of Src family protein tyrosine kinases (PTKs). It controls antigen receptor-mediated development and selection of T-lineage cells. Inactivation of the gene in immature thymocytes abrogates the requirement of preTCR, αβTCR and major histocompatibility complex (MHC) class II for the development of CD4+CD8+ double-positive and CD4+ single-positive thymocytes as well as peripheral CD4 αβT-lineage cells. TCR-MHC interactions have no impact on positive selection and commitment to the CD4 lineage in the absence of CSK. However, TCR-mediated negative selection of Csk-deficient, TCR transgenic cells is normal.
Exons 9 and 10 of these Csk mutant mice are flanked by loxP sites. Mice that are homozygous for this conditional allele are viable and fertile.
When crossed with a cre recombinase-expressing strain, these mice are useful for creating tissue-specific knockouts of the gene. Widespread deletion of expression is embryonic lethal.
For example, when bred to mice carrying Tg(Mx1-cre)1Cgn (see Stock No. 003556), interferon-induced Cre-mediated recombination results in disruption of alpha beta T cell development.
