Chimeric and molecular genetic analysis of myelin-deficient (shiverer and mld) mutant mice

Ann N Y Acad Sci. 1990:605:166-82. doi: 10.1111/j.1749-6632.1990.tb42391.x.

Abstract

The shiverer and myelin-deficient (mld) mutants are two allelic mutations. Both are characterized by hypomyelination in the CNS and deficient expression of the MBP gene. Chimeric analysis of the pathogenesis of shiverer showed that shiverer mutation acts intrinsic to the oligodendrocyte, which is the only cell type expressing the MBP gene in the CNS. Molecular genetic studies by several groups demonstrated that shiverer is a deletion mutation in the MBP gene. Consequently, no MBP is produced in the shiverer mutant. In mld, however, partial expression of the MBP gene was observed. Interestingly, MBP was expressed in a mosaic fashion in the CNS of mld mice. Molecular genetic studies revealed that the mld mutant has duplicated MBP genes in tandem on a distal part (E2-4) of chromosome 18q. The reduced expression was based on the level of mRNA. A large portion is inverted in the upstream copy, and an intact copy is located downstream. We showed in mld mutants that antisense RNA corresponding to the inverted segment is transcribed, and it forms RNA duplex, with the RNA transcribed from the normal gene located downstream.

MeSH terms

  • Animals
  • Axons / ultrastructure
  • Base Sequence
  • Brain / metabolism*
  • Brain / ultrastructure
  • Chimera
  • Crosses, Genetic
  • Female
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Neurologic Mutants / genetics*
  • Molecular Sequence Data
  • Myelin Basic Protein / genetics*
  • Myelin Sheath / ultrastructure*
  • Promoter Regions, Genetic
  • Restriction Mapping
  • Transcription, Genetic

Substances

  • Myelin Basic Protein