pp59fyn mutant mice display differential signaling in thymocytes and peripheral T cells

Paul L. Stein, Hon Man Lee, Susan Rich, Philippe Soriano

Research output: Contribution to journalArticlepeer-review

551 Scopus citations


We have generated mutant mice that do not express pp59fyn, a nonreceptor protein tyrosine kinase related to pp60src, by homologous recombination in embryonic stem cells. fyn- mice did not display an overt phenotype. Because fyn is associated with the T cell receptor (TCR), thymocyte and T cell signaling was analyzed in the mutant background. Cross-linking of TCR-CD3 in thymocytes led to markedly reduced calcium fluxes and abrogated proliferation, whereas mature splenic T cells retained largely normal proliferation despite depressed calcium movements and IL-2 production. Similarly, proliferation induced by Thy-1 cross-linking was reduced in thymocytes but not in splenic T cells. fyn- thymocytes were impaired at a late stage of maturation and showed limited clonal deletion to the Mls-1a self-superantigen but not to staphylococcal enterotoxin A. These results implicate fyn as a critical component in TCR signaling in thymocytes and, potentially, in the process that determines T cell repertoire in the adult mouse.

Original languageEnglish
Pages (from-to)741-750
Number of pages10
Issue number5
StatePublished - 4 Sep 1992
Externally publishedYes


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