ESSENTIAL ROLE OF THE TYROSINE KINASE SUBSTRATE PHOSPHOLIPASE C-GAMMA-1 IN MAMMALIAN GROWTH AND DEVELOPMENT

The activation of many tyrosine kinases leads to the phosphorylation a nd activation of phospholipase C-gamma 1 (PLC-gamma 1), To examine the biological function of this protein, homologous recombination has bee n used to selectively disrupt the Plcg1 gene in mice, Homozygous disru ption of Plcg1 results in embryonic lethality at approximately embryon ic day (E) 9.0, Histological analysis Indicates that Plcg1 (-/-) embry os appear normal at E 8.5 but fail to continue normal development and growth beyond E 8.5-E9.0. These results clearly demonstrate that PLC-g amma 1 with, by inference, its capacity to mobilize second messenger m olecules is an essential signal transducing molecule whose absence is not compensated by other signaling pathways or other genes encoding PL C isozymes.