Alopecia in a Novel Mouse Model RCO3 Is Caused by mK6irs1 Deficiency

Abstract

Reduced coat 3 (Rco3) is a new spontaneous autosomal recessive mutation with defects in hair structure and progressive alopecia. Here we describe chromosomal mapping and molecular identification of the Rco3 mutation. The murine Rco3 locus maps to a 2-Mb interval on chromosome 15 encompassing the keratin type II gene cluster. Recently, mK6irs1 was described as a type II keratin expressed in Henle's and Huxley's layer of the murine inner root sheath. Genomic sequencing revealed a 10-bp deletion in exon 1 of mK6irs1 resulting in a frameshift after 58 amino acid residues and, therefore, the absence of 422 carboxy-terminal amino acid residues containing the complete alpha-helical rod domain. Henle's and Huxley's layers show no immunoreactivity with mK6irs1-specific antibodies and the absence of intermediate filament formation in electron microscopic images. These results indicate that the expression of functional mK6irs1 is indispensable for intermediate filament formation in the inner root sheath and highlights the importance of the keratinization of the inner root sheath in the normal formation of the hair shaft.

Identification of the Rat Rex Mutation as a 7-bp Deletion at Splicing Acceptor Site of the Krt71 Gene

“…In mice, phenotypes of homozygotes for Krt71 mutations have not been described in the dominant-type mutations, while phenotype of a recessive mutant mouse, Krt71 rco3 /Krt71 rco3 , have been characterized as patchy alopecia [10]. Although Re mutation induced only 6 amino acids deletion in KRT71, it seems Re/Re phenotype would be severer than rco3/rco3 phenotype.…”

Hair follicle differentiation and regulation.

“…9), one Type II in mice (Aoki et al, 2001) and four in human (follicles) (Langbein et al, 2003). It is not known whether they specifically pair but the deficiency of one IF in the IRS through a spontaneous mutation in mice, causes collapse of the IF network and interrupts normal IRS formation (Peters et al, 2003). It would seem likely that there are more members of the IRS intermediate filament family to be found.…”

Current Genetics in Hair Diseases

“…It can be postulated that disruption of the KIF formation in the IRS results in a failure to guide the hair growth, and leads to WH phenotype. Interestingly, KRT71 mutations have also been identified in mice, rats, cats, and dogs, all of which show wavy coat phenotypes [26][27][28][29][30]. These data strongly suggest crucial roles of the IRS-specific epithelial keratins in the HF development and hair growth across mammalian species.…”