Tg(CD2-Ptpn11*C459S)1Axdr

A cDNA encoding the major transcript of mouse protein tyrosine phosphatase, non-receptor type 11 (Ptpn11; also called Shp2, src homology 2 domain-containing tyrosine phosphatase 2) with the cysteine at amino acid position 459 replaced by serine (C450S) and an N-terminal polyglutamine tag was inserted into the VA hCD2 expression cassette between the promoter and the 3' locus control region (LCR) of the human CD2 gene. Lysates of T cells, but not of B cells, from mice of this line react with antibody to polyglutamine; antibody-reactive PTPN11/SHP2 is ~7-fold higher in T-cells of transgenic than of wild-type mice. Similar expression is reported in thymus lysates. Despite a marked increase in GAB2 association of both transgene-encoded mutant and endogenous wild-type PTPN11/SHP2 in transgenic T-cells under both basal and stimulated conditions, the increase in PTPase activity that occurs in stimulated wild-type T-cells is completely abrogated, demonstrating a dominant-negative, inhibitory effect of the mutant enzyme on the activity of the wild-type enzyme. (J:105228, J:119396)