Molecular Basis for Hair Loss in Mice Carrying a Novel Nonsense Mutation (Hrrh-R) in the Hairless Gene (Hr)

• Published in: Veterinary pathology Vol. 47; no. 1; pp. 167 - 175
• Main Authors: Liu, Y, Sundberg, J.P, Das, S, Carpenter, D, Cain, K.T, Michaud, E.J, Voy, B.H
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 2010
• Subjects: Alleles; alopecia; animal disease models; Animals; Blotting, Northern; Codon, Nonsense - genetics; exons; Gene Expression Profiling; gene expression regulation; genes; Genes - genetics; genetic disorders; Hair Follicle - metabolism; hair follicles; hairless mice; histopathology; laboratory animals; messenger RNA; Mice; Mice, Hairless - genetics; microarray technology; nonsense mutation; Oligonucleotide Array Sequence Analysis; Phenotype; sequence analysis; Transcription Factors - genetics; hair follicle; hairless mice; microarray analysis; alopecia
• ISSN: 0300-9858; 1544-2217
• DOI: 10.1177/0300985809352970

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 Hrrh-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 Hrrh-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.