Endocrine Pancreas Histology of Congenic BB-Rat Strains with Reduced Diabetes Incidence After Genetic Manipulation on Chromosomes 4, 6 and X

Abstract

Congenic BB.SHR rat strains were established by crossing of spontaneously diabetic BB/OK rats and diabetes-resistant SHR rats. Chromosomal regions on which the genes Iddm 4 (BB.6s), Iddm6 (BB.Xs) and Iddm 2 (BB.LL) are located were exchanged. As a result of genetic manipulation diabetes incidence was markedly reduced from 80% in BB/OK to 50% in BB.SHR (Chr. X), to 14% in BB.SHR (Chr. 6) and to 0% in BB.LL rats. Pancreata of these newly generated BB.SHR rats were investigated histologically. In newly diagnosed diabetic rats of congenic strains pancreatic insulin content (BB.6s: p<0.05; BB.Xs p<0.01) and relative volume of insulin-positive cells (BB.Xs: p<0.001) were significantly higher than in BB/OK rats. The degree of insulitis was not different in 90-day-old and newly diagnosed diabetic animals. Surprisingly, in 30-day-old rats we observed an increase of the degree of insulitis with decreasing diabetes incidence. We suppose that by an earlier occurrence of the immunological β-cell destruction, a part of the animals is able to develop a secondary diabetes resistance. The exchange of the BB-lymphopenia gene by that of SHR-rats prevented the development of hyperglycaemia without altering the auto-reactive immune response, which could be observed in all animals investigated.

• BB rat
• Genetic manipulation
• Diabetes incidence
• Histology of pancreas