Modified composition of major ontogenetically regulated mRNAs and proteins in the cerebellum of old and of staggerer mice.

The macromolecular composition of the cerebellum was examined in young and old mice, and in staggerer mutant mice, as compared with their background control strain. We examined the in vitro translation products of cerebellum mRNA, which reflect the biosynthetic potential of cell bodies endogenous to the cerebellum. Simultaneously, we examined the composition of the major cerebellum proteins, which includes the contribution of incoming fibers, in addition to the proteins composing cerebellar cells. Changes in the concentrations of various major proteins and a significant reduction in the translational efficiency of RNA were observed in the cerebellum of old BALB/c mice. This reduction probably does not reflect a specific damage to interneurons, since RNA from the cerebellum of 5-month-old staggerer mice was as efficient in translation in vitro as RNA from the cerebellum of mice from C57B6J normal background strain. Several of the major cerebellar proteins were identified by 2-dimensional gel electrophoresis. Changes were observed at the level of and the microheterogeneity of tubulin from the cerebellum of old, as compared with young mice. The aging-related modifications in cerebellar tubulin may be regulated at the level of mRNA, since mRNA from the cerebellum of old mice appeared to produce lower amounts of a polypeptide band co-migrating with tubulin. When compared with translation products directed by mRNA from normal cerebellum, most of the major identified polypeptides produced by mRNA from staggerer cerebellum showed marked differences in their relative intensity. Thus, this mutation appears to change the composition of cerebellar mRNA. These differences were analyzed together with previously obtained data on the composition of translation products during development of normal and of irradiation-agranulated cerebellum. The combined analysis of cerebellar mRNA products permits us to tentatively assign defined protein markers to specific cerebellar cell types and periods in development.