Bahr J, Follak N, Klöting N, Wilke B, Haertel B, Klöting I
Department of Laboratory Animal Science, University of Greifswald, Karlsburg, Germany.
Exp Clin Endocrinol Diabetes. 2011 Jul;119(7):395-400. doi: 10.1055/s-0030-1270510. Epub 2011 Mar 3.
BB rats develop type 1 diabetes and WOKW rats facets of the metabolic syndrome. Both strains are common the RT1 (u) haplotype of major histocompatibility complex (MHC) which is essential for type 1 diabetes development in BB rats ( IDDM1). However, BB rats need an additional gene (lymphopenia, IDDM2, GIMAP5) to develop type 1 diabetes. Because WOKW lacks IDDM2 and does not develop hyperglycemia a congenic WOKW rat strain was generated recombining the region of chromosome 4 with IDDM2 onto the genetic background of WOKW rats (WOKW.4BB). These newly established rats and their parental WOKW rats were genetically and phenotypically characterized. Congenic WOKW.4BB rats showed a lymphopenic phenotype. The sequences of the highly polymorphic exon 2 of RT1-BB class II gene in WOKW, BB/OK, WOKW.4BB and LEW.1W rats were comparable and clearly showed the RT1 (u) haplotype. In addition, there were significant differences in metabolic traits between WOKW.4BB and parental WOKW. Although congenic WOKW.4BB rats were homozygous for IDDM1 and IDDM2 of the BB/OK rat none of WOKW.4BB rats developed hyperglycemia. This observation may be attributed to the idea that either WOKW.4BB rats need a third IDDM gene of BB/OK rats to develop hyperglycemia or WOKW background gene/s protect/s them for hyperglycemia.
BB大鼠会发展为1型糖尿病，而WOKW大鼠会出现代谢综合征的一些症状。这两种品系都具有主要组织相容性复合体（MHC）的RT1（u）单倍型，这对于BB大鼠发生1型糖尿病（IDDM1）至关重要。然而，BB大鼠需要另一个基因（淋巴细胞减少症，IDDM2，GIMAP5）才能发展为1型糖尿病。由于WOKW缺乏IDDM2且不会出现高血糖症，因此通过将4号染色体上带有IDDM2的区域重组到WOKW大鼠的遗传背景上，培育出了一种同源基因的WOKW大鼠品系（WOKW.4BB）。对这些新培育的大鼠及其亲本WOKW大鼠进行了基因和表型特征分析。同源基因的WOKW.4BB大鼠表现出淋巴细胞减少的表型。WOKW、BB/OK、WOKW.4BB和LEW.1W大鼠中RT1 - BB II类基因高度多态的外显子2序列具有可比性，并且清楚地显示出RT1（u）单倍型。此外，WOKW.4BB与亲本WOKW在代谢特征上存在显著差异。尽管同源基因的WOKW.4BB大鼠对于BB/OK大鼠的IDDM1和IDDM2是纯合的，但没有一只WOKW.4BB大鼠出现高血糖症。这一观察结果可能归因于以下观点：要么WOKW.4BB大鼠需要BB/OK大鼠的第三个IDDM基因才能出现高血糖症；要么WOKW背景基因保护它们不发生高血糖症。
