title: Kyoto rhino rats derived by ENU mutagenesis undergo congenital hair loss and exhibit focal glomerulosclerosis.
abstract: N-ethyl-N-nitrosourea (ENU) mutagenesis is an important tool for studying gene function and establishing human disease models. Here, we report the characterization of a novel hairless mutant rat strain that carries a recessive mutation called Kyoto rhino (krh), which was created by ENU-mutagenesis. We produced a F344-krh strain through inbreeding without backcrossing to F344 rats. The krh/krh rats lost their coat hair by eight weeks of age. They also developed wrinkled skin, cystic hair canals and long curved nails by four months of age. Markedly dilated hair follicles that contained keratin debris were observed during histological analysis of the skin. The krh locus was mapped near the hairless (Hr) gene on chromosome 15. Sequence analysis revealed a nonsense mutation (c. 1238 C>A, p. S413X) in the Hr gene. The truncated HR protein was deduced to lack a zinc-finger domain and repression domains. In aged Hr(krh)/Hr(krh) rats, focal glomerulosclerosis (FGS) was observed in which collapsed glomeruli contained protein exudates in Bowman's capsule. Mesangial matrices that had proliferated in segments and foot processes that were fused in podocytes were also observed. The Hr(krh)/Hr(krh) rats also suffered from significant proteinuria. Given its breeding history, the F344-Hr(krh) strain may harbor ENU-induced mutation(s) that underlie FGS in addition to having the Hr(krh) mutation. The F344-Hr(krh) rat is a useful model of skin disease and may provide a new model system for the examination of the pathogenesis of FGS.
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuramoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.forename: Fumi
authors.initials: F
authors.lastname: Tagami
authors.forename: Tomoji
authors.initials: T
authors.lastname: Mashimo
authors.forename: Masato
authors.initials: M
authors.lastname: Nose
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
mesh_terms: D000505:Alopecia / Q000235:genetics; D000818:Animals; D018389:Codon, Nonsense; D005038:Ethylnitrosourea; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics*; D006801:Humans; D008297:Male; D016296:Mutagenesis; D010641:Phenotype; D051381:Rats; D054772:Rats, Hairless / Q000235:genetics*; D011916:Rats, Inbred F344; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D005038:Ethylnitrosourea