RESUMO
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.
Assuntos
Etilnitrosoureia , Glomerulosclerose Segmentar e Focal/genética , Mutagênese , Ratos Pelados/genética , Alopecia/genética , Animais , Códon sem Sentido , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Masculino , Fenótipo , Ratos , Ratos Endogâmicos F344 , Dedos de Zinco/genéticaRESUMO
In order to establish a system to facilitate the systematic collection, preservation, and provision of laboratory rats (Rattus norvegicus) and their derivates, the National BioResource Project-Rat (NBRP-Rat) was launched in July 2002. By the end of 2008, more than 500 rat strains had been collected and preserved as live animals, embryos, or sperm. These rat resources are supplied to biomedical scientists in Japan as well as in other countries. This review article introduces NBRP-Rat and highlights the phenome project, recombinant inbred strains, BAC clone libraries, and the ENU-mutant archive, named the Kyoto University Rat Mutant Archive (KURMA). The future direction of rat resources are also discussed.
