Progressive hair loss and myocardial degeneration in rough coat mice: Reduced lysyl oxidase-like (LOXL) in the skin and heart

Abstract

The rough coat (re) is a spontaneous recessive mutation in mice. To identify the mutated gene, we have characterized the re phenotype and initiated linkage mapping. The re mice show growth retardation, cyclic and progressive hair loss, hyperplastic epidermis, abnormal hair follicles, cardiac muscle degeneration, and reduced amount of collagen and elastin in the skin and heart. The rc locus was mapped at 32.0 cM on chromosome 9, close to the loxl gene. Lysyl oxidase-like (LOXL) protein is a novel copper-containing amine oxidase that is required for the cross-linking of elastin and collagen in vitro. LOXL is expressed at high levels in the skin and heart, where the re mice show strong phenotype. The expression pattern and the genetic proximity to rc suggested loxl as a potential candidate gene. In re mice, the loxl mRNA was reduced in the skin and the LOXL protein in the heart, dermis, atrophic hair follicles, and sebaceous glands. No mutations, however, were identified within the coding region of loxl, and offspring from re/re and loxl null mice crossing were phenotypically normal. Based on these results, loxl appears non-allelic to rc. Heart- and skin-specific downregulation of LOXL in re mice, however, may contribute to the extracellular matrix alterations and the re phenotype.