Journal Article

Mutation at the <i>Anophthalmia White</i> Locus in Syrian Hamsters: Hploinsufficiency in the <i>Mitf</i> Gene Mimics Human Waardenburg Syndrome Type 2

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

in Human Molecular Genetics

Volume 7, issue 4, pages 703-708
Published in print April 1998 | ISSN: 0964-6906
Published online April 1998 | e-ISSN: 1460-2083 | DOI:
Mutation at the Anophthalmia White Locus in Syrian Hamsters: Hploinsufficiency in the Mitf Gene Mimics Human Waardenburg Syndrome Type 2

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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.

Journal Article.  4081 words.  Illustrated.

Subjects: Genetics and Genomics

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