Buse J B, Ben-Nun A, Klein K A, Eisenbarth G S, Seidman J G, Jackson R A
Diabetes. 1984 Jul;33(7):700-3. doi: 10.2337/diab.33.7.700.
The BB rat spontaneously develops insulin-dependent diabetes mellitus of autoimmune etiology. From breeding studies, one of the genes necessary for the development of diabetes in these animals is linked to RT1, the rat major histocompatibility complex. To better define the BB rat's RT1-linked diabetogenic gene (RT1-DM), we have used restriction endonucleases BamH1 and EcoR1 in conjunction with an I-A alpha (class II mouse major histocompatibility complex) gene probe to study RT1 class II gene polymorphisms among diabetes-prone BB rats and the related non-diabetes-prone BBN rats. Both BB and BBN rats are indistinguishable RT1u by serologic methods. Four polymorphic chromosome types (la, lb, lla, and llb) were recognized among the control BBN rats. In contrast, all BB rats were homozygous (lla/lla). From the multiple breeding programs involved, we hypothesize that the BB rat's RT1-linked diabetogenic gene is linked to an l-A alpha-defined gene of the type lla chromosome. The ability to split the RT1u of BB rats will provide a powerful tool to localize and characterize RT1-DM.
BB大鼠会自发发生自身免疫病因的胰岛素依赖型糖尿病。通过繁殖研究发现,这些动物发生糖尿病所需的基因之一与大鼠主要组织相容性复合体RT1相关。为了更好地界定与BB大鼠RT1相关的致糖尿病基因(RT1-DM),我们使用了限制性内切酶BamH1和EcoR1,并结合I-Aα(II类小鼠主要组织相容性复合体)基因探针,来研究易患糖尿病的BB大鼠和相关的不易患糖尿病的BBN大鼠之间的RT1 II类基因多态性。通过血清学方法,BB大鼠和BBN大鼠在RT1u方面无法区分。在对照BBN大鼠中识别出四种多态性染色体类型(la、lb、lla和llb)。相比之下,所有BB大鼠都是纯合子(lla/lla)。从所涉及的多个繁殖计划来看,我们推测BB大鼠与RT1相关的致糖尿病基因与lla染色体类型的由I-Aα界定的基因相关。能够区分BB大鼠的RT1u将为定位和鉴定RT1-DM提供一个强大的工具。