Changes in the pattern of expression of pp60c-src in cerebellar mutants of mice

Cultures of neurons from rat embryos have been shown previously to express high levels of a unique form of pp60c-src [Brugge et al (1985): Nature 316:524-526], the cellular homologue of the transforming protein of Rous sarcoma virus. This altered form of pp60c-src, designated pp60c-src(+), displays a retarded electrophoretic mobility due to a structural alteration within the aminoterminal region of the molecule [Brugge et al, 1985]. In order to investigate the distribution and possible role of pp60c-src(+) in intact brain, we have examined the expression of pp60c-src(+) in extracts from developing cerebella from wild-type mice and mutant mice that display progressive degeneration of specific classes of cerebellar neurons. The loss of pp60c-src(+) generally correlated with the loss of granule cells and Purkinje cells from the cerebella of mice carrying the staggerer (sg/sg) and Lurcher (Lc/+) mutations, with the most pronounced changes observed in cerebella from the more severely affected sg/sg mice. The expression of pp60c-src(+) in weaver wv/wv mice is qualitatively and quantitatively quite different. From the earliest time points, there was a significant reduction in the levels of pp60c-src(+), with no further loss of this form during the period of maximal neuronal differentiation. This suggests an early, predegenerative absence of pp60c-src(+) in this mutant strain, which is defective in granule-cell migration.