A novel autosomal recessive mutant was produced using N-ethyl-N-nitrosourea mutagenesis. The characteristics of the mutant mice included progressive irreversible hair loss within a month of birth, wrinkled skin, and long curved nails. Linkage analysis revealed that the causative gene is linked to D14Mit193 on chromosome 14. Sequence analysis of the complete cDNA of the candidate gene, hairless (Hr), identified a homozygous G-to-T transition at nucleotide 3572, leading to the substitution of glycine by tryptophan, designated Gly960Trp. This missense mutation occurs in the vicinity of repression domain 3 of the hairless protein (HR). This allele was named Hrm1Enu. The relative amounts of Hr mRNA and HR protein determined by real-time PCR and Western blot analyses, respectively, were slightly elevated in the mutant mice. Quantitative real-time PCR analysis revealed the increased expression of Kc1 and Vdr in the mutant mice, whereas the expression of Nrs1 and Krtap16-6 was decreased. These results suggest that the Gly960Trp substitution in HR protein in Hrm1Enu mice may alter the function of HR as a transcriptional corepressor.
Bibliographical noteFunding Information:
This study was supported by 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 the Basic Science Research Program (KRF-2003-015-C00540) from the Korea Research Foundation to S.J. Kim. We thank Dr. Catherine C. Thompson who kindly provided the HR specific anti-serum.
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