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Animal Bioresource in Japan

.: Home > Animal Bioresource in Japan > 2011 > Volume 60 Number 1 > Takashi KURAMOTO1), Mitsuru KUWAMURA2), Fumi TAGAMI1), Tomoji MASHIMO1), Masato NOSE3) and Tadao SERIKAWA1)

Kyoto Rhino Rats Derived by ENU Mutagenesis Undergo Congenital Hair Loss and Exhibit Focal Glomerulosclerosis

Takashi KURAMOTO1), Mitsuru KUWAMURA2), Fumi TAGAMI1), Tomoji MASHIMO1), Masato NOSE3) and Tadao SERIKAWA1)
1) Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University 2) Laboratory of Veterinary Pathology, Osaka Prefecture University 3) Department of Pathogenomics, Graduate School of Medicine, Ehime University
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 Hrkrh/Hrkrh 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 Hrkrh/Hrkrh rats also suffered from significant proteinuria. Given its breeding history, the F344-Hrkrh strain may harbor ENU-induced mutation(s) that underlie FGS in addition to having the Hrkrh mutation. The F344-Hrkrh rat is a useful model of skin disease and may provide a new model system for the examination of the pathogenesis of FGS.

Keywords :
disease model, hairless, mutation, nephrosis

Date Deposited : 21 Jun 2011 11:16

Last Modified : 21 Jun 2011 11:16

Official URL: http://www.jstage.jst.go.jp/browse/expanim/60/1/_contents

Volume 60, Number 1, - 2011

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