Mutation at the anophthalmic white locus in Syrian hamsters: Haploinsufficiency in the Mitf gene mimics human Waardenburg syndrome type 2

Colin A. Hodgkinson, Atsuo Nakayama, Hua Li, Lori Beth Swenson, Karin Opdecamp, James H. Asher, Heinz Arnheiter, Thomas M Glaser

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Mutations in MITF (microphthalmia transcription factor) cause Waardenburg syndrome type 2 (WS2A) in humans, an autosomal dominant disorder consisting of deafness and hypopigmentation. Phenotypes vary significantly within WS2 pedigrees, and there is generally no correlation between the predicted biochemical properties of mutant MITF proteins and disease severity, We have identified a nonsense mutation in the Mitf gene of the anophthalmic white (Wh) Syrian hamster that destabilizes its mRNA and prevents the encoded basic helix-loop-helix leucine zipper (bHLHzip) protein from dimerizing or binding DNA target sites. Although the resulting polypeptide does not act as a dominant-negative species in vitro, the Wh mutation is inherited as a semi-dominant trait. It thus more closely resembles WS2 than comparable Mitf alleles in laboratory mice and rats, which are expressed as purely recessive traits.

Original languageEnglish (US)
Pages (from-to)703-708
Number of pages6
JournalHuman Molecular Genetics
Volume7
Issue number4
DOIs
StatePublished - Apr 1998
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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