Cloning and developmental expression analysis of the murine homolog of the spinocerebellar ataxia type 1 gene (Sca1)

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominantneurodegenerative disorder caused by the expansion of a CAG trinucleotiderepeat which encodes glutamine in the novel protein ataxin-1. In order tocharacterize the developmental expression pattern of SCA1 and to identifyputative functional domains in ataxin-1, the murine homolog (Sca1) wasisolated. Cloning and characterization of the murine Sca1 gene revealedthat the gene organization is similar to that of the human gene. The murineand human ataxin-1 are highly homologous but the CAG repeat is virtuallyabsent in the mouse sequence suggesting that the polyglutamine stretch isnot essential for the normal function of ataxin-1 in mice. Cellular anddevelopmental expression of the murine homolog was examined using RNA insitu hybridization. During cerebellar development, there is a transientburst of Sca1 expression at postnatal day 14 when the murine cerebellarcortex becomes physiologically functional. There is also marked expressionof Sca1 in mesenchymal cells of the intervertebral discs during developmentof the spinal column. These results suggest that the normal Sca1 gene, hasa role at specific stages of both cerebellar and vertebral columndevelopment.