Sundström, Elisabeth
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
Abstract
SummaryGreying with age in horses is an autosomal dominant trait, characterized by hair greying, high incidence of melanoma and vitiligo-like depigmentation. Previous studies have revealed that the causative mutation for this phenotype is a 4.6-kb intronic duplication in STX17 (Syntaxin 17). By using reporter constructs in transgenic zebrafish, we show that a construct containing two copies of the duplicated sequence acts as a strong enhancer in neural crest cells and has subsequent melanophore-specific activity during zebrafish embryonic development whereas a single copy of the duplicated sequence acts as a weak enhancer, consistent with the phenotypic manifestation of the mutation in horses. We further used luciferase assays to investigate regulatory regions in the duplication, to reveal tissue-specific activities of these elements. One region upregulated the reporter gene expression in a melanocyte-specific manner and contained two microphthalmia-associated transcription factor (MITF) binding sites, essential for the activity. Microphthalmia-associated transcription factor regulates melanocyte development, and these binding sites are outstanding candidates for mediating the melanocyte-specific activity of the element. These results provide strong support for the causative nature of the duplication and constitute an explanation for the melanocyte-specific effects of the Grey allele.
Published in
Pigment Cell and Melanoma Research
2012, volume: 25, number: 1, pages: 28-36
SLU Authors
Andersson, Leif
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
UKÄ Subject classification
Genetics and Breeding in Agricultural Sciences
Publication identifier
- DOI: https://doi.org/10.1111/j.1755-148X.2011.00902.x
Permanent link to this page (URI)
https://res.slu.se/id/publ/43629