Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Exp Anim. 2010;59(2):147-55. doi: 10.1538/expanim.59.147.
To collect rat mutations and increase the value of the rat model system, we introduced fancy-derived mutations to the laboratory and carried out genetic analyses. Six fancy rats were shipped from a fancy rat colony in the USA and used as founders. After initial crosses with a laboratory strain, TM/Kyo or PVG/Seac, inbreeding started and 6 partially inbred lines, including 2 sublines, were produced as Kyoto Fancy Rat Stock (KFRS) strains. During inbreeding, we isolated 9 mutations: 5 coat colors, American mink (am), Black eye (Be), grey (g), Pearl (Pel), siamese (sia); 1 coat pattern, head spot (hs); 2 coat textures, Rex (Re), satin (sat); and an ear pinnae malformation, dumbo (dmbo). Genetic analyses mapped 7 mutations to particular regions of the rat chromosomes (Chr): am to Chr 1, sia to Chr 1, sat to Chr 3, Re to Chr 7, g to Chr 8, dmbo to Chr 14, and hs to Chr 15. Candidate gene analysis revealed that a missense mutation in the tyrosinase gene, Ser79Pro, was responsible for sia. From mutant phenotypes and mapping positions, it is likely that all mutations isolated in this study were unique to the fancy rat. These findings suggest that fancy rat colonies are a good source for collecting rat mutations. The fancy-derived mutations, made available to biomedical research in the current study, will increase the scientific value of laboratory rats.
为了收集大鼠突变并提高大鼠模型系统的价值，我们将奇特来源的突变引入实验室并进行了遗传分析。从美国的一个奇特大鼠群体中引入了 6 只奇特大鼠作为创始者。与实验室品系 TM/Kyo 或 PVG/Seac 进行初步杂交后，开始近交，产生了 6 条部分近交系，包括 2 个子系，作为京都奇特大鼠品系（KFRS）。在近交过程中，我们分离出了 9 个突变：5 种毛色，美洲水貂（am）、黑眼睛（Be）、灰色（g）、珍珠（Pel）、暹罗（sia）；1 种毛色模式，头斑（hs）；2 种毛色纹理，卷毛（Re）、缎子（sat）；和 1 种耳翼畸形，短耳（dmbo）。遗传分析将 7 个突变定位到大鼠染色体的特定区域（Chr）：am 到 Chr1，sia 到 Chr1，sat 到 Chr3，Re 到 Chr7，g 到 Chr8，dmbo 到 Chr14，hs 到 Chr15。候选基因分析表明，酪氨酸酶基因中的错义突变 Ser79Pro 是 sia 的原因。从突变表型和定位位置来看，本研究中分离的所有突变很可能是奇特大鼠所特有的。这些发现表明奇特大鼠群体是收集大鼠突变的良好来源。当前研究中提供给生物医学研究的奇特衍生突变将增加实验室大鼠的科学价值。
