Construction of a mouse model of Charcot-Marie-Tooth disease type 1A by pronuclear injection of human YAC DNA

Hum Mol Genet. 1996 May;5(5):563-9. doi: 10.1093/hmg/5.5.563.


Construction of animal models of human inherited diseases is particularly important for testing gene therapy approaches. Towards this end, we constructed a mouse model for Charcot-Marie-Tooth disease type 1A by pronuclear injection of a YAC containing the human PMP22 gene. In one transgenic line, the YAC DNA is integrated in about eight copies and the PMP22 gene is strongly expressed to give a peripheral neuropathy closely resembling the human pathology. The disorder is dominant, causes progressive weakness of the hind legs, and there is severe demyelination in the peripheral nervous system including the presence of onion bulb formations. This approach will be valuable for pathologies produced by over-expression of a gene including trisomy and amplification in cancer. Such models will be particularly useful for testing gene therapy approaches if the transgene is human.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Charcot-Marie-Tooth Disease / genetics*
  • Chromosome Mapping
  • Chromosomes, Artificial, Yeast / genetics*
  • Disease Models, Animal*
  • Female
  • Gene Expression Regulation
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Mice, Transgenic
  • Microinjections
  • Microscopy, Electron
  • Molecular Sequence Data
  • Myelin Proteins / genetics*
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Sciatic Nerve / chemistry
  • Sciatic Nerve / ultrastructure
  • Tissue Distribution


  • Myelin Proteins
  • PMP22 protein, human
  • Pmp22 protein, mouse
  • RNA, Messenger

Associated data

  • GENBANK/D11428
  • GENBANK/M32240