Genetic predisposition to insulin-dependent diabetes mellitus (IDDM) involves one or more loci within the class II region of the major histocompatibility complex (MHC). The strongest MHC-linked determinants of disease susceptibility have been associated with polymorphisms in both the $ alpha$ and $ beta$ chain subunits of HLA-DQ (human) and I-A (mouse) class II molecules. Specifically, protection against IDDM development is associated with the presence of aspartic acid at position 57 of the $ beta$ chain while non-aspartic acid residues are found in diabetogenic $ beta$ chains. In humans, the greatest risk of disease development is observed in individuals with Arg 52$ rm sp+ alpha/Asp 57 sp- beta$ heterodimers. The BB rat is a useful system in which one can identify and characterize the genes necessary for the onset of IDDM. Although sequence data have been reported for various alleles of these class II genes, the effect of polymorphisms in the rat MHC is not nearly as well characterized as it is in humans or the NOD mouse. The rat MHC (RT1) contains two expressed class II loci, RT1.B and RT1.D, each encoding two class II molecules: RT1.B $ alpha$ and $ beta,$ and RT1.D $ alpha$ and $ beta.$ This study determined the nucleotide sequences of relevant regions from the RT1.B and RT1.D $ alpha/ beta$ genes in five rat strains (ACI, BB, Buffalo, Lewis, and Wistar-Furth) of varying susceptibility to IDDM to examine the role of specific polymorphisms in predisposition to disease. The data show that BB and Wistar-Furth rats (RT1$ sp{ rm u}$ haplotype) have identical class II sequences at all of the regions examined. Although no unique $ alpha$ chain sequences were found to associate with IDDM, we did confirm the association of aspartic acid at position 57 of RT1.B$ beta$ with susceptibility to diabetes. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.27390 |
| Date | January 1996 |
| Creators | Pointer, Rohan. |
| Contributors | Finks, Abraham (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001549293, proquestno: MQ29765, Theses scanned by UMI/ProQuest. |
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