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

Sandro Banfi, Antonio Servadio, Ming Yi Chung, Fiorentino Capozzoli, Lisa A. Duvick, Robert Elde, Huda Y. Zoghbi, Harry T. Orr

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Abstract

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat which encodes glutamine in the novel protein ataxin-1. In order to characterize the developmental expression pattern of SCA1 and to identify putative functional domains in ataxin-1,the murine homolog (Sca1) was isolated. Cloning and characterization of the murine Sca1 gene revealed that the gene organization is similar to that of the human gene. The murine and human ataxin-1 are highly homologous but the CAG repeat is virtually absent in the mouse sequence suggesting that the polyglutamine stretch is not essential for the normal function of ataxin-1 in mice. Cellular and developmental expression of the murine homolog was examined using RNA in situ hybridization. During cerebellar development, there is a transient burst of Sca1 expression at postnatal day 14 when the murine cerebellar cortex becomes physiologically functional. There is also marked expression of Sca1 in mesenchymal cells of the intervertebral discs during development of the spinal column. These results suggest that the normal Sca1 gene, has a role at specific stages of both cerebellar and vertebral column development.

Original languageEnglish (US)
Pages (from-to)33-40
Number of pages8
JournalHuman molecular genetics
Volume5
Issue number1
DOIs
StatePublished - Jan 1996

Bibliographical note

Funding Information:
This work was supported by grants from the National Institutes of Health, National Institute of Neurological Disease and Stroke (NS27699 to H.Y.Z and NS33718 to H.T.O.) and by a fellowship from Italian Telethon to A.S.

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