Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Åke Lernmark

Principal investigator

Default user image.

Diabetes resistance in the BB rat maps to a body weight regulator on chromosome 2

Author

  • L. S. Klaff
  • G. Koike
  • J. Jiang
  • Y. Wang
  • S. Bieg
  • A. Pettersson
  • E. Lander
  • H. Jacob
  • Å Lernmark

Summary, in English

Insulin-dependent Type 1 diabetes mellitus is the most common chronic disorder in children and young adults. The genetics, etiology and pathogenesis is complicated by the apparent presence of several genetic region; that contribute to susceptibility. The genetic dissection of Type 1 autoimmune diabetes in the inbred BioBreeding (BB) rat which closely resembles the human disorder was shown to involve two genes: iddm1, which mapped to the lymphopenia (lyp) region on chromosome 4 and iddm2, which mapped to RT1u in the major histocompatibility complex (MHC) on chromosome 20. A cross-intercross analysis between BB rats and Fischer rats revealed a third factor, iddm3, which confers diabetes resistance. We now report the successful mapping of iddm3 by crossing non-diabetic lyp/lyp-u/u (BBxFischer) F2 rats (3/486 or 0.6% developed diabetes) with lyp/lyp-u/u diabetic BB rats. 40/89 (45%) of these F2 back-cross rats did not develop diabetes. A complete genome scan showed that the Fischer resistance factor (iddm3) was linked to a 4 cM region on chromosome 2 flanked by D2Mit15 and D2Mgh29 (lod score 7.68). Using these markers in a second (BBxFischer) F2 cross (n=279), homozygosity of the BB allele (n=40) for iddm3 was associated with a greater weight reduction after fasting than the homozygosity of the Fischer allele (n=52) (p< 0.008). In conclusion, the development of Type 1 diabetes in the BB rat is controlled by three genes: lymphopenia, MHC and a third factor, iddm3 that may be related to metabolism and body weight regulation.

Publishing year

1999-01-01

Language

English

Pages

2-2

Publication/Series

Journal of Investigative Medicine

Volume

47

Issue

2

Document type

Conference paper: abstract

Publisher

Lippincott Williams & Wilkins

Status

Published

ISBN/ISSN/Other

  • ISSN: 1708-8267