Progressive Hair Loss and Myocardial Degeneration in Rough Coat Mice: Reduced Lysyl Oxidase-Like (LOXL) in the Skin and Heart

Abstract

The rough coat (rc) is a spontaneous recessive mutation in mice. To identify the mutated gene, we have characterized the rc phenotype and initiated linkage mapping. The rc 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 rc mice show strong phenotype. The expression pattern and the genetic proximity to rc suggested loxl as a potential candidate gene. In rc 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 rc/rc 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 rc mice, however, may contribute to the extracellular matrix alterations and the rc phenotype.

Genetic ablation of myelin protein zero-like 3 in mice increases energy expenditure, improves glycemic control, and reduces hepatic lipid synthesis

“…However, full alopecia was reported in Mpzl3 rc mice greater than 1 yr of age (7,21). Several other phenotypic changes were noted in Mpzl3 rc mice, including elevated blood calcium levels and myocardial fiber degeneration (21). Our studies failed to find these differences 14 C]acetate, and lipids were extracted with a 2:1 mixture of chloroform-methanol.…”

“…Furthermore, none of the mice we examined between 1 and 2 yr of age had complete fur loss; nor were significant differences in the extent of fur loss noted between KO mice that were 1-2 yr old. However, full alopecia was reported in Mpzl3 rc mice greater than 1 yr of age (7,21). Several other phenotypic changes were noted in Mpzl3 rc mice, including elevated blood calcium levels and myocardial fiber degeneration (21).…”

“…These mice have been characterized by their unkempt coat and progressive alopecia (12,36). Additionally, male Mpzl3 rc mice at 12 wk were reported to have a 10% reduction in body weight (21). In the present work, we utilized gene targeting in mice to delineate the in vivo metabolic function of MPZL3.…”

The Role of Lysyl Oxidase-like 2 in the Odontogenic Differentiation of Human Dental Pulp Stem Cells

“…These are known as LOX, LOXL, LOXL2, LOXL3, and LOXL4 in humans (Kagan et al, 1995). Each LOX family protein contains a copper-binding motif, lysyl-tyrosyl-quinone (LTQ) residues, and a cytokine receptor-like (CRL) domain in its highly conserved carboxyl (C)-terminus (Hayashi et al, 2004a). The main molecular function of the LOX enzyme is lysyl oxidation to make protein cross-linking through lysine residues.…”

Lysyl oxidase-like 3 mRNA expression indicates poor survival from oral squamous cell carcinoma

“…5 A recent study indicated that the downregulation of LOX-L1 in skin and heart of mice may produce the rough coat (rc) phenotype from a spontaneous mutation. 20 However, the oncogenic potential of LOX-L1 was rarely Figure 3 The distribution of normalized mRNA expression level of LOXL genes in tissue pairs. The statistical analysis is summarized in Table 3.…”