Genetic variation in the multifunctional transcription factor Yy1 and type 1 diabetes mellitus in the BB rat

Molecular Genetics and Metabolism
Nora Klöting, I Klöting

Abstract

Spontaneous diabetes in B(io)B(reeding) rats is complex, polygenic, and recessively inherited. Several crossing studies have demonstrated that beside the class II genes of the major histocompatibility complex (MHC, Iddm1) additional non-MHC genes are involved in diabetes development. One of them, Iddm4, was initially mapped on chromosome 6q32. To study the physiologic importance of Iddm4 a congenic BB.SHR rat strain (BB.6S) was established. The BB.6S is characterised by a drastic reduction of diabetes frequency (86 vs. 14%) indicating existence of diabetes protective genes of SHR on the exchanged chromosomal segment. One of the possible diabetes susceptibility candidate genes located within this exchanged region is the multifunctional transcription factor Yin yang 1 (Yy1). Yy1 was therefore sequenced in BB/OK and SHR rats. No genetic variation in exons between BB/OK and SHR was found. However, three single nucleotide polymorphisms (SNPs) were detected in intron 4. To determine the "wild type" allele, intron 4 of several diabetes-resistant inbred rat strains (DA, LEW, BN, and WOKW) and wild rats was sequenced. In addition, a congenic BB/OK strain was established by introgressing the same segment of chromosome 6 (D6Rat184-D6Rat3)...Continue Reading

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Citations

Jun 1, 2005·Biochemical and Biophysical Research Communications·Nora Klöting, Ingrid Klöting
Feb 1, 2011·Transplant Immunology·Jeanette BahrNiels Follak
Dec 19, 2006·Diabetes/metabolism Research and Reviews·Nora KlötingIngrid Klöting
Sep 17, 2004·Biochemical and Biophysical Research Communications·Nora Klöting, Ingrid Klöting
May 13, 2006·Clinical Science·Yang Yang, Pere Santamaria
Mar 27, 2019·Proceedings of the National Academy of Sciences of the United States of America·Peng GaoKai Tan

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