Abstract
Two new diabetic strains, C57BL/KsJ-db 2J and C57BL/6J-db 2J, have been developed. C57BL/KsJ-db 2J/db2J mice are indistinguishable from C57BL/KsJ-db/db mice, the original diabetes mutation. Both have severe diabetes characterized by hyperphagia, obesity, marked hyperglycemia, temporarily elevated plasma insulin concentrations, and typical degenerative changes in the islets of Langerhans. In contrast, C57BL/6J-db 2J/db2J mice, although also hyperphagic and obese, have mild diabetes characterized by transitory hyperglycemia and markedly elevated plasma insulin concentrations coupled with marked hypertrophy of the islets and increased proliferative capacity of beta cells. The mild diabetes-like syndrome produced by diabetes-2J on the C57BL/6J background is similar to that produced by the obese gene (ob) on the same background. The islet responses, whether atrophy or hypertrophy, appear to be due to the interaction of diabetes-2J (and possibly obese) with modifiers in the genetic background rather than being peculiar to the specific mutant. The markedly different disease patterns that result when the same gene is placed on different inbred backgrounds emphasize the importance of strict genetic control in biochemical and physiological studies with these and other obesity mutants.
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Supported in part by NIH Research Grants AM 14461 from the National Institute of Arthritis and Metabolic Diseases; CA 05873 from the National Cancer Institute; ACS E-162, a Janice M. Blood Memorial Grant for Cancer Research from the American Cancer Society; GB 27487 from the National Science Foundation; and an allocation from the Southwaite Foundation.
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Hummel, K.P., Coleman, D.L. & Lane, P.W. The influence of genetic background on expression of mutations at the diabetes locus in the mouse. I. C57BL/KsJ and C57BL/6J strains. Biochem Genet 7, 1–13 (1972). https://doi.org/10.1007/BF00487005
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DOI: https://doi.org/10.1007/BF00487005