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

Klaff, L. S. ; Koike, G. ; Jiang, J. ; Wang, Y. ; Bieg, S. ; Pettersson, A. ; Lander, E. ; Jacob, H. and Lernmark, Å LU orcid (1999) In Journal of Investigative Medicine 47(2). p.2-2
Abstract

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... (More)

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.

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author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Journal of Investigative Medicine
volume
47
issue
2
pages
2 - 2
publisher
BMJ Publishing Group
external identifiers
  • scopus:33750107446
ISSN
1708-8267
language
English
LU publication?
no
id
3973f661-cb98-411e-9d15-35fd7758ea9e
date added to LUP
2019-06-25 13:17:54
date last changed
2022-01-31 22:34:29
@misc{3973f661-cb98-411e-9d15-35fd7758ea9e,
  abstract     = {{<p>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 RT1<sup>u</sup> 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&lt; 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.</p>}},
  author       = {{Klaff, L. S. and Koike, G. and Jiang, J. and Wang, Y. and Bieg, S. and Pettersson, A. and Lander, E. and Jacob, H. and Lernmark, Å}},
  issn         = {{1708-8267}},
  language     = {{eng}},
  month        = {{01}},
  note         = {{Conference Abstract}},
  number       = {{2}},
  pages        = {{2--2}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Journal of Investigative Medicine}},
  title        = {{Diabetes resistance in the BB rat maps to a body weight regulator on chromosome 2}},
  volume       = {{47}},
  year         = {{1999}},
}