Molecular basis for hair loss in mice carrying a novel nonsense mutation (Hrrh-R ) in the hairless gene (Hr).

Document Type

Article

Publication Date

2010

Keywords

Animals, Blotting-Northern, Codon-Nonsense, Gene-Expression-Profiling, Genes, Hair-Follicle, Mice, Mice-Hairless, Oligonucleotide-Array-Sequence-Analysis, Phenotype, Transcription-Factors

First Page

167

Last Page

176

JAX Location

see Reprint Collection (a pdf is available).

JAX Source

Vet Pathol 2010 Jan; 47(1):167-76.

Abstract

Animal models carrying mutations in the hairless (Hr) gene provide a rich resource for study of hair follicle biology. A spontaneous mouse mutant with a phenotype strikingly similar to rhino mutants of Hr arose spontaneously in the mouse facility at Oak Ridge National Laboratory. Sequence analysis of Hr in these mutants uncovered a nonsense mutation in exon 12, designated as Hr(rh-R) (rhino, Oak Ridge). The mutation led to significant reduction in Hr mRNA levels, predicted to be due to nonsense-mediated decay. Histological analysis indicated dilated hair follicle infundibula at 14 days of age that rapidly became filled with cornified material. Microarray analyses revealed that expression levels of many genes involved in keratinocyte differentiation, epidermal regeneration, and wound healing were significantly upregulated before morphological detection of the phenotype, suggesting their role in onset of the Hr(rh-R) phenotype. Identification of this new Hr allele and the underlying molecular alterations allows further understanding of the role of Hr in hair follicle biology.

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