The Cdb:BHE Rat--A Model for Non-Insulin-Dependent, Nonobese Diabetes Mellitus

Abstract

The Cdb:BHE stock is a subline of the parent BHE stock now housed in the Genetic Resource Unit, National Center for Research Resources, National Institutes of Health (NIH). The parent stock was developed some 50 years ago by scientists at what was then called the Bureau of Home Economics (Adams, 1964). The stock was named BHE in honor of the bureau, which was an early predecessor of the present day Beltsville Human Nutrition Research Center of the U. S. Department of Agriculture (USDA). The parental stock is the result of a cross between hooded Osborne-Mendel rats, called Yale at that time, and rats of the now extinct albino Pennsylvania State College stock. Progeny of this cross were albino, all black, all brown, black and white, brown and white, or agouti. Once the cross was made, the colony was maintained as a closed colony. Fulland half-sibling matings were avoided, as were backcrosses. In the mid-1960s, M. W. Marshall et al. (Marshall and Lehmann, 1967; Marshall et al., 1969a, b, 1971, 1976) developed a number of sublines. Backcrosses and fullsibling matings were used to produce lines of BHE rats that were lean, obese, and/or had renal disease due to a variety of lesions. One of these lines was hyperglycemic and developed a renal pathology similar to that observed in humans with diabetes mellitus. None of these sublines now exist; however, they are of interest because they document the presence of genes for each of these characteristics in the parental BHE stock. In 1975, the development of the Cdb:BHE subline began. Breeding stock was selected for the presence of hyperlipemia and hyperglycemia and the absence of obesity and hydronephrosis. Full-sibling matings and backcrosses were used to strengthen the appearance of the hyperlipemic/hyperglycemic trait. Following 36 generations of selection, 75 percent of the rats showed hyperlipemia and hyperglycemia at 300 days of age, but not at 100 days of age. For the last 10 generations, full-sibling matings have been avoided, and the colony is maintained by random breeding. A full genetic history back to 1975