THE PROTEIN-TYROSINE KINASE P60(C-SRC) IS NOT IMPLICATED IN THE PATHOGENESIS OF THE HUMAN AUTOSOMAL RECESSIVE FORM OF OSTEOPETROSIS - A STUDY OF 13 CHILDREN

Osteopetrosis has been described in mice generated by homozygous gene disruption of c-src gene encoding for the p60(c-Src) protein tyrosine kinase (Src(-/-) mice). The similarities of bone histologic findings i n this murine model to those observed in some patients first seen with autosomal recessive osteopetrosis, ''malignant'' osteopetrosis, led u s to investigate the potential role of p60(c-Src) in the pathogenesis of malignant osteopetrosis in 13 children. In 4 patients a c-src mutat ion was ruled out by an intragenic microsatellite segregation study. I n the other 9 we analyzed p60(c-Src) expression and function, as well as c-src sequence. The expression was normal in all of the patients te sted. In addition, the tyrosine phosphorylation and kinase activity of p60(c-Src) were also normal in all of the patients. Moreover, in thes e patients, sequences of the coding region of c-src were identical to the published sequence of the human c-src complementary DNA. These res ults exclude a role for c-src in the pathogenesis of human malignant o steopetrosis in the 13 patients analyzed.