P0-Cre Transgenic Mice for Inactivation of Adhesion Molecules in Schwann Cells

Ann N Y Acad Sci. 1999 Sep 14;883:116-23.

Abstract

Normal peripheral nerve myelination depends on Schwann cell-basal lamina interactions. An important component of Schwann cell basal lamina is laminin--predominantly laminins 2 and 4. Mutations in the alpha 2 chain common to these two isoforms are associated with dysmyelination in mouse (dy) and man (congenital muscular dystrophy). Thus, laminin 2 and 4 receptors are also likely to be important for myelin formation. Several laminin 2/4 receptors are detected at the basal lamina surface of myelin-forming Schwann cells, namely, alpha 6 beta 4 and alpha 6 beta 1 integrins and dystroglycan. The evidence linking these receptors to myelination is suggestive, but not conclusive. Genetic studies have not yet confirmed a role for these molecules in myelin formation. Natural or targeted inactivation of alpha 6, beta 4, and beta 1 integrins and of dystroglycan have profound effects on other tissues causing embryonic or perinatal death before myelination. Therefore, to conditionally inactivate these receptors specifically in myelin-forming Schwann cells, we have constructed and initially characterized a P0-Cre transgene that activates Cre-mediated recombination of loxP-containing genes in peripheral nerve.

Publication types

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

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Humans
  • Integrases / genetics
  • Integrases / metabolism*
  • Laminin / physiology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Myelin P0 Protein / genetics
  • Myelin P0 Protein / physiology*
  • Organ Specificity
  • Receptors, Laminin / deficiency
  • Receptors, Laminin / genetics
  • Receptors, Laminin / physiology*
  • Recombinant Proteins / metabolism
  • Schwann Cells / physiology*
  • Sciatic Nerve / physiology
  • Sciatic Nerve / ultrastructure
  • Viral Proteins*
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism

Substances

  • Laminin
  • Myelin P0 Protein
  • Receptors, Laminin
  • Recombinant Proteins
  • Viral Proteins
  • Cre recombinase
  • Integrases
  • beta-Galactosidase