Morphologic and molecular characterization of two novel Krt71 (Krt2-6g) mutations: Krt71 rco12 and Krt71 rco13

Abstract

We have analyzed two novel mouse mutant strains, Rco12 and Rco13, displaying a wavy pelage and curly vibrissae that have been identified in an ENU screen for dominant mutations affecting the pelage. The mutations were mapped to mouse Chromosome 15 and identified as missense point mutations in the first exon of the Krt71 (formerly called Krt2-6g) gene causing alterations of amino acid residue 143 from alanine to glycine (Rco12) and residue 146 from isoleucine to phenylalanine. The morphologic analyses demonstrated that both mutations cause identical phenotypes leading to the formation of filamentous aggregates in Henle's and Huxley's layers of the inner root sheath (IRS) of the hair follicle that leads to the bending of the hair shaft. Both novel mutations are located in the immediate vicinity of previously identified mutations in murine Krt71 that cause similar phenotypes and alter the helix initiation motif of the keratin. The characterization of these mutants demonstrates the importance of this Krt71 domain for the formation of linear IRS intermediate filaments.

A Missense Mutation within the Helix Initiation Motif of the Keratin K71 Gene Underlies Autosomal Dominant Woolly Hair/Hypotrichosis

“…Of these, substitutions from Phe to Cys at this amino-acid position have been found in K1 and K6A proteins as pathogenic mutations for epidermolytic hyperkeratosis and pachyonychia congenita type 1, respectively (Virtanen et al, 2001;Liao et al, 2007) (Supplementary Table S1 online). In addition, all dominant mutations in the KRT71 gene responsible for wavy coat phenotype in mice have been identified in either the HIM or HTM of K71 protein (Kikkawa et al, 2003;Runkel et al, 2006;Shimomura et al, 2010b) (Figure 3a).…”

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

“…Missense mutations at positions 143 and 146, such as Rco12 and Rco13, also result in curly body hair [11]. A single nucleotide polymorphism (SNP) causing a non-synonymous alteration (Arg151Trp) has been recently identified to be associated with curly hair in dogs [3].…”

“…Among them, keratin 71 (Krt71) (previously, K6irs1 or Krt2-6g) is a good candidate because Krt71-mutant mice display wavy pelage and curly vibrissae, which are inherited in an autosomal dominant manner [6,11]. This prompted us to investigate nucleotide alterations in the Krt71 gene of KFRS5A/Kyo rats.…”

Hairless Plays a Role in Formation of Inner Root Sheath via Regulation of Dlx3 Gene

“…Type I IRS keratin genes, i.e. Krt25, Krt27, and Krt28, and type II IRS keratin gene Krt71 are the keratins specifically expressed in all three layers of IRS and known to support the structures of IRS (34,35). We observed that expression of these IRS keratins was affected consistently by Hr, both in vivo and in vitro.…”