Abstract
Genodermatoses, such as heritable skin disorders, mostly represent Mendelian conditions. Congenital hypotrichosis (HY) characterize a condition of being born with less hair than normal. The purpose of this study was to characterize the clinicopathological phenotype of a breed-specific non-syndromic form of HY in Hereford cattle and to identify the causative genetic variant for this recessive disorder. Affected calves showed a very short, fine, wooly, kinky and curly coat over all parts of the body, with a major expression in the ears, the inner part of the limbs, and in the thoracic-abdominal region. Histopathology showed a severely altered morphology of the inner root sheath (IRS) of the hair follicle with abnormal Huxley and Henle’s layers and severely dysplastic hair shafts. A genome-wide association study revealed an association signal on chromosome 5. Homozygosity mapping in a subset of cases refined the HY locus to a 690 kb critical interval encompassing a cluster of type II keratin encoding genes. Protein-coding exons of six positional candidate genes with known hair or hair follicle function were re-sequenced. This revealed a protein-changing variant in the KRT71 gene that encodes a type II keratin specifically expressed in the IRS of the hair follicle (c.281delTGTGCCCA; p.Met94AsnfsX14). Besides obvious phenocopies, a perfect concordance between the presence of this most likely pathogenic loss-of-function variant located in the head domain of KRT71 and the HY phenotype was found. This recessive KRT71-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002114-9913).
Highlights
The growing hair shaft is molded by the inner root sheath (IRS), which is surrounded by the companion layer, the outer root sheath, and the fibrous sheath
No abnormalities in dentition were noticed as previously seen in cattle affected by ectodermal dysplasia, which is characterized by sparse hair and abnormal teeth [44]
The examination of the integument of both calves showed very short, fine, wooly, kinky and curly hair when compared to healthy animals (Figure 1a–c)
Summary
Hair is one of the distinguishing characteristics of mammals, and is involved in a wide range of functions such as thermoregulation, physical protection, and sensory activity [1]. The hair follicle (HF) is responsible for the production of hair [2,3,4]. The HF represents an ectodermal appendage of the skin and is a complex structure [5]. The growing hair shaft is molded by the inner root sheath (IRS), which is surrounded by the companion layer, the outer root sheath, and the fibrous sheath. The IRS is composed of three layers: the IRS cuticle, the Huxley layer, and the Henle layer [6]. Many genes and signaling are known to be involved in HF development [1]
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