Genetic analysis of the BB/W diabetic rat

Abstract

A large colony of BB/W diabetic rats was developed as a research model for insulin dependent, type 1 diabetes mellitus. The foundation stock had 8% diabetics which appeared in a sporadic manner. The Worcester (W) colony was inbred by brother .times. sister matings for 11 generations and the proportion of diabetics increased to over 50%. The age of detection varies from 46-250 days. For selection purposes, classification was made at 120 days, which means that 15-20% of potential diabetics were classified as normal. Evidence from different analyses indicates that the inheritance of diabetes is by a recessive gene or gene cluster with 50% penetrance at 120 days. The selection of breeding stock from diabetic parents raised the proportion of diabetics produced by 2 normal parents from 12-43%. Diallel tests show that diabetic and normal offspring of 2 diabetic parents have the same diabetic genotype. Outcrosses to other strains of rat indicate that the trait is transferred as a recessive with only 3% diabetics recovered in the F2 where noninbred BB stock was used as the diabetic source, and 36% where partially inbred BB/W was used as the diabetic parent. Since the proportion of diabetics produced by all types of crosses has changed, and may continue to change with changes in the genetic background, the operational term penetrance was used to describe the frequency of diabetes in individuals homozygous for the diabetes gene cluster. At present the penetrance at 120 days is 59% in the BB/W colony.