Genetic studies of IDDM in BB rats: the incidence of diabetes in F2 and first backcross hybrids allows rejection of the recessive hypothesis.
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 1.A) F1, F2 generations and of first backcross hybrids onto BB (B1BB) and LEW.1A (B1A) 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 B1A 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 B1BB hybrids was 13.8% (BB/OK) and 24.0% (BB/PhiK) respectively. All diabetic hybrids were characterized by at least one RT1uv 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Klöting
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Central Institute of Diabetes Gerhardt Katsch, Karlsburg/GDR.
Stark
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D000818:Animals; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006239:Haplotypes; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB / Q000235:genetics*; D011919:Rats, Inbred Strains / Q000235:genetics*