IMPAIRED DEVELOPMENT OF CD4(-(KNOCK-IN) INTO FYN LOCUS() CD8(+) THYMOCYTES BY CSK)

p59(fyn) is one of the Src-family kinases thought to play an important role in signaling through T cell receptor, However, Fyn deficiency ha s caused no overt defects in vivo on T cell development, nor has it ca used any changes in the phosphorylation status of molecules such as ZA P-70 which have been proposed as p59(fyn) substrates, This could be ex plained as being due to compensation of Fyn deficiency by other Src-fa mily kinases, Here, we have 'knocked-in' the csk gene, a negative regu lator of Src-family kinases, into fyn locus to challenge the problem o f redundant functions among Src-family kinases, The csk-'knock-in' mic e displayed atrophy of the thymic cortex and impaired development of C D4(+) CD8(+) thymocytes, This was concomitant with decrease in tyrosin e phosphorylation of ZAP-70 and p120(cbl).