Diabetes resistance in the BB rat maps to a body weight regulator on chromosome 2
(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.
(Less)
- author
- Klaff, L. S.
; Koike, G.
; Jiang, J.
; Wang, Y.
; Bieg, S.
; Pettersson, A.
; Lander, E.
; Jacob, H.
and Lernmark, Å
LU
- publishing date
- 1999-01-01
- 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< 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}}, }