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A Small Deletion Hotspot in the Type II Keratin Gene mK6irs1/Krt2-6g on Mouse Chromosome 15, a Candidate for Causing the Wavy Hair of the Caracul ( Ca ) Mutation

2003; Oxford University Press; Volume: 165; Issue: 2 Linguagem: Inglês

10.1093/genetics/165.2.721

1943-2631

Yoshiaki Kikkawa, Ayumi Oyama, Rie Ishii, Ikuo Miura, Takashi Amano, Yoshiyuki Ishii, Yasuhiro Yoshikawa, Hiroshi Masuya, Shigeharu Wakana, Toshihiko Shiroishi, Choji Taya, Hiromichi Yonekawa,

melanin and skin pigmentation

Abstract A new mutation has arisen in a colony of mice transgenic for human α-galactosidase. The mutation is independent of the transgenic insertion, autosomal dominant, and morphologically very similar to the classical wavy coat mutation, caracul (Ca), on chromosome 15. Therefore, we designated this locus the caracul Rinshoken (CaRin). Applying a positional cloning approach, we identified the mK6irs1/Krt2-6g gene as a strong candidate for CaRin because among five Ca alleles examined mutations always occurred in the highly conserved positions of the α-helical rod domain (1A and 2B subdomain) of this putative gene product. The most striking finding is that four independently discovered alleles, the three preexistent alleles CaJ, Ca9J, Ca10J, and our allele CaRin, all share one identical amino acid deletion (N 140 del) and the fifth, CamedJ, has an amino acid substitution (A 431 D). These findings indicate that a mutation hotspot exists in the Ca locus. Additionally, we describe a Ca mutant allele induced by ENU mutagenesis, which also possesses an amino acid substitution (L 424 W) in the mK6irs1/Krt2-6g gene. The identification of the Ca candidate gene enables us to further define the nature of the genetic pathway required for hair formation and provides an important new candidate that may be implicated in human hair and skin diseases.