Genetic Studies of IDDM in BB Rats: The Incidence of Diabetes in F₂ and First Backcross Hybrids Allows Rejection of the Recessive Hypothesis³)

Summary

The BB rat spontaneously develops an IDDM with many analogies to human IDDM, i.e. the genetic basis is a puzzle, since more than one mode of inheritance of IDDM in BB rats has been proposed. These different proposals reflect the heterogeneity of BB rats used for genetic studies. This prompted us to investigate the inheritance of IDDM in two subpopulations of BB rats (BB/OK and BB/PhiK) by crossing studies with the production of (diabetic BB x LEW l.A) F₁,F₂ generations and of first backcross hybrids onto BB (B_1BB) and LEW.1A (B_1A) rats respectively. Both BB rat subpopulations were different in origin, degree of inbreeding, incidence and age at onset of diabetes and in certain immunologic, metabolic and hematologic traits. All hybrids were serotyped and checked for diabetes by determination of urine and plasma glucose twice weekly up to an age of 200 days. — None of the F₁ and B_1A hybrids developed diabetes. Some cases were observed in the F₂ hybrids with a different incidence in the two subpopulations (2.3% in BB/OK, 11.0% in BB/PhiK). The percentage of diabetes in the B_1BB hybrids was 13.8% (BB/OK) and 24.0% (BB/PhiK) respectively. All diabetic hybrids were characterized by at least one RT1^UV haplotype which was derived from the original BB animals. These results demonstrated clearly (1) that the mode of inheritance depends on the genotype of the animals observed and (2) simple autosomal-recessive genetics cannot be accepted for BB rat diabetes. The only way to gain deeper insight into the mode of inheritance of BB rat diabetes is to develop inbred lines and congenic derivatives of BB rats in order to isolate the diabetogenic genes or gene complexes.

Key words

IDDM - BB rat - Genetics - MHC