Kyoto Rhino Rats Derived by ENU Mutagenesis Undergo Congenital Hair Loss and Exhibit Focal Glomerulosclerosis
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概要
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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 Bowmans 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.
著者
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庫本 高志
Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University
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SERIKAWA Tadao
Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University
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桑村 充
大阪府立大学 大学院生命環境科学研究科獣医病理学教室
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NOSE Masato
Department of Pathogenomics, Ehime University Graduate School of Medicine
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KURAMOTO Takashi
Institute of Laboratory Animals, Faculty of Medicine, Kyoto University
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KUWAMURA Mitsuru
Laboratory of Veterinary Pathology, Osaka Prefecture University
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TAGAMI Fumi
Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University
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MASHIMO Tomoji
Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University
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桑村 充
Laboratory of Veterinary Pathology, Osaka Prefecture University
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田上 史
Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University
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Serikawa Tadao
Institute For Laboratory Animals Faculty Of Medicine Kyoto University
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Mashimo Tomoji
Institute Of Laboratory Animals Faculty Of Medicine Kyoto University
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庫本 高志
京都大学大学院医学研究科附属動物実験施設
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Kuramoto Takashi
Carcinogenesis Division National Cancer Center Research Institute
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Kuramoto Takashi
Institute Of Laboratory Animals Faculty Of Medicine Kyoto University
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Nose Masato
Department Of Internal Medicine Division Of Nephrology And Rheumatology Aichi Medical University Sch
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庫本 高志
京都大学 大学院医学研究科 附属動物実験施設
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