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

Hum Mol Genet. 1996 Jan;5(1):33-40. doi: 10.1093/hmg/5.1.33.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Ataxin-1
  • Ataxins
  • Base Sequence
  • Cerebral Cortex / chemistry
  • Cerebral Cortex / embryology
  • Cerebral Cortex / growth & development
  • Embryonic and Fetal Development
  • Gene Expression Regulation, Developmental*
  • Humans
  • Intervertebral Disc / cytology
  • Intervertebral Disc / embryology
  • Mesoderm / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Purkinje Cells / chemistry
  • RNA, Messenger / analysis
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid*
  • Spinal Cord / chemistry
  • Spinocerebellar Degenerations / genetics*
  • Trinucleotide Repeats / genetics*

Substances

  • ATXN1 protein, human
  • Ataxin-1
  • Ataxins
  • Atxn1 protein, mouse
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • RNA, Messenger

Associated data

  • GENBANK/X83542