HETEROGENEOUS EXPRESSION OF NEUROFILAMENT PROTEINS IN FOREBRAIN AND CEREBELLUM DURING DEVELOPMENT - CLINICAL IMPLICATIONS FOR SPINOCEREBELLAR ATAXIA

Using quantitative immunoblotting, we have measured the level of two m ammalian neurofilament proteins, the 68-kDa NF-L and the 66-kDa NF-66 (alpha-internexin), in the rat CNS during development. NF-66 is locali zed in neurons and neuronal processes in both embryonic and postnatal brain. Importantly, NF-66 is more abundant than NF-L in both forebrain and cerebellum during development. The prevalence of NF-66 over NF-L is most pronounced in brain gray matter. The expression of both NF-66 and NF-L increases continuously during the first month after birth. In situ hybridization demonstrated that N-66, but not NF-L, is expressed in the cerebellar granule cells. Our findings suggest that the neurof ilaments are heterogeneous in developmental expression, among neuronal subtypes and in composition. Human NF-66 neurofilament has recently b een mapped to chromosome 10q24. Careful analysis of the human genome m ap indicates NF-66 gene lies within the critical region of infantile-o nset spinocerebellar ataxia (IOSCA). The characteristic developmental expression and spatial localization of the NF-66 gene suggests it as a candidate gene for the disease. (C) 1997 Elsevier Science B.V.