The spastic mouse: aberrant splicing of glycine receptor beta subunit mRNA caused by intronic insertion of L1 element

Neuron. 1994 Oct;13(4):1003-15. doi: 10.1016/0896-6273(94)90265-8.

Abstract

Mice homozygous for the spastic mutation (spa) suffer from a complex motor disorder resulting from reduced CNS levels of the adult glycine receptor isoform GlyRA, which is composed of ligand-binding alpha 1 and structural beta polypeptides. The beta subunit-encoding gene (Glyrb) was mapped near the spa locus on mouse chromosome 3. In spa/spa mice, aberrant splicing of the beta subunit pre-mRNA strikingly diminishes the CNS contents of full-length transcripts, whereas truncated beta subunit mRNAs accumulate. This is a result of exon skipping, which causes translational frameshifts and premature stop codons. Intron 5 of the spa Glyrb gene contains an L1 transposable element that apparently is causal for the aberrant splicing of beta subunit transcripts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Cloning, Molecular
  • DNA Transposable Elements
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Introns*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Muscle Spasticity / genetics*
  • Mutation*
  • RNA Precursors / genetics
  • RNA Splicing*
  • RNA, Messenger / genetics*
  • Receptors, Glycine / genetics*

Substances

  • DNA Transposable Elements
  • DNA, Complementary
  • RNA Precursors
  • RNA, Messenger
  • Receptors, Glycine

Associated data

  • GENBANK/X81201
  • GENBANK/X81202
  • GENBANK/X81203
  • GENBANK/X81204