Mouse models for four types of Waardenburg syndrome

Pigment Cell Res. 2003 Oct;16(5):448-54. doi: 10.1034/j.1600-0749.2003.00066.x.

Abstract

Waardenburg syndrome (WS) is an auditory-pigmentary syndrome caused by a deficiency of melanocytes and other neural crest-derived cells. Depending on a variety of symptoms associated with the auditory-pigmentary symptoms, WS is classified into four types: WS type 1 (WS1), WS2, WS3, and WS4. Six genes contributing to this syndrome--PAX3, SOX10, MITF, SLUG, EDN3 and EDNRB--have been cloned so far, all of them necessary for normal development of melanocytes. Mutant mice with coat color anomalies were helpful in identifying these genes, although the phenotypes of these mice did not necessarily perfectly match those of the four types of WS. Here we describe mice with mutations of murine homologs of WS genes and verify their suitability as models for WS with special interest in the cochlear disorder. The mice include splotch (Sp), microphthalmia (mi), Slugh-/-, WS4, JF1, lethal-spotting (ls), and Dominant megacolon (Dom). The influence of genetic background on the phenotypes of mice mutated in homologs of WS genes is also addressed. Finally, possible interactions among the six WS gene products are discussed.

Publication types

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

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • Disease Models, Animal*
  • High Mobility Group Proteins / genetics
  • Mice
  • Mice, Mutant Strains
  • Microphthalmia-Associated Transcription Factor
  • Mutation*
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Pigments, Biological / genetics
  • Receptor, Endothelin B / genetics
  • SOXE Transcription Factors
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Waardenburg Syndrome / classification
  • Waardenburg Syndrome / genetics*

Substances

  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Pigments, Biological
  • Receptor, Endothelin B
  • SOXE Transcription Factors
  • Snai2 protein, mouse
  • Snail Family Transcription Factors
  • Sox10 protein, mouse
  • Transcription Factors
  • Pax3 protein, mouse