A mutation in the Cdon gene potentiates congenital nevus development mediated by NRAS(Q61K)

Pigment Cell Melanoma Res. 2016 Jul;29(4):459-64. doi: 10.1111/pcmr.12487.

Abstract

Congenital nevi develop before birth and sometimes cover large areas of the body. They are presumed to arise from the acquisition of a gene mutation in an embryonic melanocyte that becomes trapped in the dermis during development. Mice bearing the Cdk4(R24C) ::Tyr-NRAS(Q) (61K) transgenes develop congenital nevus-like lesions by post-natal day 10, from melanocytes escaping the confines of hair follicles. We interbred these mice with the collaborative cross (CC), a resource that enables identification of modifier genes for complex diseases (those where multiple genes are involved). We examined variation in nevus cell density in 66 CC strains and mapped a large-effect quantitative trait locus (QTL) controlling nevus cell density to murine chromosome 9. The best candidate for a gene that exacerbates congenital nevus development in the context of an NRAS mutation is Cdon, a positive regulator of sonic hedgehog (Shh) that is expressed mainly in keratinocytes.

Keywords: Congenital nevi; Qtl; mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / genetics*
  • Cells, Cultured
  • Dermis / metabolism
  • Dermis / pathology
  • Female
  • GTP Phosphohydrolases / genetics*
  • Hair Follicle / metabolism
  • Hair Follicle / pathology
  • Humans
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Male
  • Melanocytes / metabolism
  • Melanocytes / pathology*
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Knockout
  • Mutation*
  • Nevus / congenital*
  • Nevus / pathology
  • Skin Neoplasms / congenital*
  • Skin Neoplasms / pathology

Substances

  • Cdon protein, mouse
  • Cell Adhesion Molecules
  • Membrane Proteins
  • GTP Phosphohydrolases
  • NRAS protein, human