Iddm1 and Iddm2 Homozygous WOK.4BB Rats Develop Lymphopenia, but no Hyperglycemia like the BB/OK Rats

Abstract

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.

Key words

type 1 diabetes - metabolic syndrome - congenics - hyperglycemia - MHC class II gene

References

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