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A novel mutation in Hr causes abnormal hair follicle morphogenesis in hairpoor mouse, an animal model for Marie Unna Hereditary Hypotrichosis

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Abstract

Hairpoor mice (Hr Hp) were derived through N-ethyl-N-nitrosourea (ENU) mutagenesis. These mice display sparse and short hair in the Hr Hp/+ heterozygous state and complete baldness in the Hr Hp/Hr Hp homozygous state. This phenotype was irreversible and was inherited in an autosomal semidominant manner. Hair follicles (HFs) of Hr Hp/+ mice underwent normal cycling and appeared normal, although smaller than those of the wild-type mice. In contrast, HFs of Hr Hp/Hr Hp mice became cyst-like structures by postnatal day (P) 21. The number and length of vibrissae decreased in a dose-dependent manner as the number of mutant alleles increased. A positional candidate gene approach was used to identify the gene responsible for the hairpoor phenotype. Genetic linkage analysis determined that the hairpoor locus is 2 cm from D14Mit34 on chromosome 14. Sequence analysis of the exons of the candidate gene hairless revealed a T-to-A transversion mutation at nucleotide position 403 (exon 2), presumably resulting in abolishment of an upstream open reading frame (uORF). In addition, we also found that the near-naked mouse (Hr N), a spontaneously arising mutant, harbors a A402G transition in its genome. Both mutations were in the uATG codon of the second uORF in the 5′ UTR and corresponded to the mutations identified in Marie Unna Hereditary Hypotrichosis (MUHH) patients. In the present study we describe the phenotype, histological morphology, and molecular etiology of an animal model of MUHH, the hairpoor mouse.

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Acknowledgments

This study was supported by a grant from the National Research Laboratory Program (2000-N-NL-01-c-207) of the Ministry of Science and Technology of Korea awarded to C.W. Song and by a grant from the Basic Science Research Program (KRF-2003-015-C00540) from the Korea Research Foundation to S.J. Kim.

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Authors and Affiliations

  1. Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Science, Department of Biomedical Sciences, The Catholic University of Korea, 505, Banpo 4 dong, Seochogu, Seoul, 137-701, Korea

    In Cheol Baek, Jeong Ki Kim, Jong Keun Park & Sungjoo Kim Yoon

  2. Laboratory of Toxicogenomics, Korea Institute of Toxicology, Taejon, 305-600, Korea

    Kyu-Hyuk Cho, Dal-Sun Cha, Jae-Woo Cho & Chang-Woo Song

Authors
  1. In Cheol Baek
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  2. Jeong Ki Kim
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  3. Kyu-Hyuk Cho
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  4. Dal-Sun Cha
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  5. Jae-Woo Cho
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  6. Jong Keun Park
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  7. Chang-Woo Song
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  8. Sungjoo Kim Yoon
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Corresponding author

Correspondence to Sungjoo Kim Yoon.

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I. C. Baek and J. K. Kim contributed equally to this work.

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Supplementary material 1 (XLS 24 kb)

335_2009_9191_MOESM2_ESM.tif

Supplementary Fig. 1 Genotyping D14Mit34 by PCR-SSLP. C57BL6, 158 bp; BALB/c, 138 bp. The hairpoor-causing gene was localized at 2 cM away from D14Mit34 (TIF 2466 kb)

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Baek, I.C., Kim, J.K., Cho, KH. et al. A novel mutation in Hr causes abnormal hair follicle morphogenesis in hairpoor mouse, an animal model for Marie Unna Hereditary Hypotrichosis. Mamm Genome 20, 350–358 (2009). https://doi.org/10.1007/s00335-009-9191-8

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