Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons

Cell. 1992 Nov 13;71(4):565-76. doi: 10.1016/0092-8674(92)90591-y.


We have used homologous recombination in embryonic stem cells to generate mice carrying a mutation in the gene encoding P0, an immunoglobulin-related recognition molecule and the major protein of peripheral nervous system myelin. These mice are deficient in normal motor coordination and exhibit tremors and occasional convulsions. Axons in their peripheral nerves are severely hypomyelinated and a subset of myelin-like figures and axons degenerate. The mutation leads to an abnormal regulation of some, but not all, molecules involved in myelination. These results demonstrate that P0 is essential for the normal spiraling, compaction, and maintenance of the peripheral myelin sheath and the continued integrity of associated axons. They further suggest that this protein conveys a signal that regulates Schwann cell gene expression.

Publication types

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

MeSH terms

  • Animals
  • Axons / ultrastructure*
  • Base Sequence
  • Blotting, Southern
  • Blotting, Western
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Demyelinating Diseases / genetics*
  • Demyelinating Diseases / pathology
  • Gene Expression Regulation / genetics
  • Mice
  • Microscopy, Electron
  • Molecular Sequence Data
  • Mutagenesis, Insertional / genetics
  • Myelin P0 Protein
  • Myelin Proteins / genetics*
  • Myelin Sheath / ultrastructure*
  • Restriction Mapping
  • Schwann Cells / ultrastructure*
  • Seizures / genetics
  • Seizures / pathology
  • Tremor / genetics
  • Tremor / pathology


  • Cell Adhesion Molecules, Neuronal
  • Myelin P0 Protein
  • Myelin Proteins