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.
A new mutation has arisen in a colony of mice transgenic for human alpha-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 (Ca(Rin)). Applying a positional cloning approach, we identified the mK6irs1/Krt2-6g gene as a strong candidate for Ca(Rin) because among five Ca alleles examined mutations always occurred in the highly conserved positions of the alpha-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 Ca(J), Ca(9J), Ca(10J), and our allele Ca(Rin), all share one identical amino acid deletion (N 140 del) and the fifth, Ca(medJ), 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.
Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science (Rinshoken), Tokyo 113-8613, Japan.
Yoshiaki
Y
Kikkawa
Ayumi
A
Oyama
Rie
R
Ishii
Ikuo
I
Miura
Takashi
T
Amano
Yoshiyuki
Y
Ishii
Yasuhiro
Y
Yoshikawa
Hiroshi
H
Masuya
Shigeharu
S
Wakana
Toshihiko
T
Shiroishi
Choji
C
Taya
Hiromichi
H
Yonekawa
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006197:Hair / Q000502:physiology*; D007150:Immunohistochemistry; D007633:Keratins / Q000235:genetics* / Q000502:physiology; D053564:Keratins, Hair-Specific; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D020161:Physical Chromosome Mapping; D017384:Sequence Deletion
C456200:KRT71 protein, human; D053564:Keratins, Hair-Specific; D007633:Keratins