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Original Articles

NIDDM Genes in Mice: Deleterious Synergism by Both Parental Genomes Contributes to Diabetogenic Thresholds

  1. Edward H Leiter,
  2. Peter C Reifsnyder,
  3. Kevin Flurkey,
  4. Hans-Joachim Partke,
  5. Erika Junger and
  6. Lieselotte Herberg
  1. Jackson Laboratory Bar Harbor, Maine
  2. Diabetes Research Institute Düsseldorf, Germany
  1. Address correspondence and reprint requests to Dr. Edward H. Leiter, The Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609. E-mail: ehl{at}aretha.jax.org
Diabetes 1998 Aug; 47(8): 1287-1295. https://doi.org/10.2337/diab.47.8.1287
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Abstract

We used mouse genetics to model how polygenic thresholds for the transition from impaired glucose tolerance (IGT) to NIDDM are reached. NON/Lt and NZO/Hl are inbred mouse strains selected for IGT and polygenic obesity, respectively. Their Fl male progeny consistently developed NIDDM. Genetic analysis of F2 males from both cross directions identified an NON-derived diabetogenic locus, Nidd 1, on chromosome (Chr) 4 near the leptin receptor. This locus was associated with reduced plasma insulin, increased non-fasted blood glucose, and lower body weight. Another NON-derived diabetogenic locus on Chr 18 (Nidd2) that controls blood glucose was identified. An NZO-derived diabetogenic region on Chr 11 (Nidd3), possibly comprising two separate loci, reduced ability to sustain elevated plasma insulin and significantly reduced weight gain over time. Thus, the diabetogenic synergism between genetic loci from strains separately exhibiting subthreshold defects perturbing glucose homeostasis underscores the likely complexity of the inheritance of obesity-associated forms of NIDDM in humans.

  • Received March 6, 1998.
  • Revision received April 29, 1998.
  • Accepted April 29, 1998.
  • Copyright © 1998 by the American Diabetes Association

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August 1998, 47(8)
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NIDDM Genes in Mice: Deleterious Synergism by Both Parental Genomes Contributes to Diabetogenic Thresholds
Edward H Leiter, Peter C Reifsnyder, Kevin Flurkey, Hans-Joachim Partke, Erika Junger, Lieselotte Herberg
Diabetes Aug 1998, 47 (8) 1287-1295; DOI: 10.2337/diab.47.8.1287

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NIDDM Genes in Mice: Deleterious Synergism by Both Parental Genomes Contributes to Diabetogenic Thresholds
Edward H Leiter, Peter C Reifsnyder, Kevin Flurkey, Hans-Joachim Partke, Erika Junger, Lieselotte Herberg
Diabetes Aug 1998, 47 (8) 1287-1295; DOI: 10.2337/diab.47.8.1287
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