title: A novel missense mutation in the mouse hairless gene causes irreversible hair loss: genetic and molecular analyses of Hr m1Enu.
abstract: 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 Hr(m1Enu). 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 Hr(m1Enu) mice may alter the function of HR as a transcriptional corepressor.
authors.affiliation: Laboratory of Toxicogenomics, Korea Institute of Toxicology, Taejon 305-600, Korea.
authors.forename: YoonYi
authors.initials: Y
authors.lastname: Nam
authors.forename: Jeong Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Dal-Sun
authors.initials: DS
authors.lastname: Cha
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Cho
authors.forename: Kyu-Hyuk
authors.initials: KH
authors.lastname: Cho
authors.forename: SeokJoo
authors.initials: S
authors.lastname: Yoon
authors.forename: Jong-Bok
authors.initials: JB
authors.lastname: Yoon
authors.forename: Yang-Seok
authors.initials: YS
authors.lastname: Oh
authors.forename: Jun-Gyo
authors.initials: JG
authors.lastname: Suh
authors.forename: Sang-Seop
authors.initials: SS
authors.lastname: Han
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Song
authors.forename: SungJoo Kim
authors.initials: SK
authors.lastname: Yoon
mesh_terms: D000483:Alleles; D000505:Alopecia / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D017124:Conserved Sequence; D003433:Crosses, Genetic; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005038:Ethylnitrosourea / Q000494:pharmacology; D005808:Genes, Recessive; D008040:Genetic Linkage; D006239:Haplotypes; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009153:Mutagens / Q000494:pharmacology; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*; D014364:Tryptophan / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D018076:DNA, Complementary; D009153:Mutagens; D012333:RNA, Messenger; D014157:Transcription Factors; C088661:hr protein, mouse; D014364:Tryptophan; D005038:Ethylnitrosourea