Locus on chromosome 18 cosegregates with diabetes in the BB/OK rat subline.

Diabete & metabolisme Pub Date : 1995-12-01
I Klöting, L Vogt, T Serikawa
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Abstract

The spontaneously diabetic BB rat is a well-established animal model of human insulin-dependent diabetes mellitus. Besides the lymphopenia gene (Iddm 1) and the MHC class-II genes of the RT1u haplotype (Iddm 2), at least one other non-MHC gene (Iddm 3) is considered essential for diabetes development. To investigate the participation of this third gene in the development of diabetes in our BB/OK rat subline, we analysed 119 [(BB/OK x DA)F1 x BB/OK] first backcross hybrids phenotypically and genotypically. Genotyping with 5 classical and 28 polymorphic microsatellite markers indicated that the third gene is located on chromosome 18, about 22 +/- 7 cM distal from the Olf locus (Iod score = 2.33). Significantly more diabetics than Iddm 1 and Iddm 2 homozygous nondiabetic subjects were homozygous for this locus. Interacting genes located on chromosomes X and/or 1 seem to be involved.

在BB/OK大鼠亚系中,18号染色体位点与糖尿病共分离。
自发性糖尿病大鼠是人类胰岛素依赖型糖尿病的动物模型。除了淋巴细胞减少基因(Iddm 1)和RT1u单倍型的MHC ii类基因(Iddm 2)外,至少还有一个非MHC基因(Iddm 3)被认为对糖尿病的发展至关重要。为了研究这第三个基因在我们的BB/OK大鼠亚系中糖尿病发展中的作用,我们分析了119个[(BB/OK x DA)F1 x BB/OK]第一次回交杂种的表型和基因表型。5个经典微卫星标记和28个多态微卫星标记的基因分型表明,第3基因位于18号染色体上,距离黄位点约22 +/- 7 cM (Iod评分= 2.33)。与Iddm 1和Iddm 2纯合子的非糖尿病受试者相比,糖尿病患者在该位点上的纯合子显著增加。位于染色体X和/或1上的相互作用基因似乎也参与其中。
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