BB rat diabetes susceptibility and body weight regulation genes colocalize on Chromosome 2
(1999) In Mammalian Genome 10(9). p.883-887- Abstract
The genetic etiology of Type 1 (insulin-dependent) diabetes mellitus is complicated by the apparent presence of several diabetes susceptibility genetic regions. Type I diabetes in the inbred BioBreeding (BB) rat closely resembles the human disorder and was previously shown to involve two genes: the lymphopenia (lyp) region on Chromosome (Chr) 4 and RT1(u) in the major histocompatibility complex (MHC) on Chr 20. In addition, a segregation analysis of an F2 intercross between the diabetes-prone congenic BB DR(lyp/lyp,u/u) and F344(+/+,lv/lv) rats indicated that at least one more genetic factor was responsible for Type 1 diabetes. In this study, we generated F2N2 progeny in a cross between non-diabetic... (More)
The genetic etiology of Type 1 (insulin-dependent) diabetes mellitus is complicated by the apparent presence of several diabetes susceptibility genetic regions. Type I diabetes in the inbred BioBreeding (BB) rat closely resembles the human disorder and was previously shown to involve two genes: the lymphopenia (lyp) region on Chromosome (Chr) 4 and RT1(u) in the major histocompatibility complex (MHC) on Chr 20. In addition, a segregation analysis of an F2 intercross between the diabetes-prone congenic BB DR(lyp/lyp,u/u) and F344(+/+,lv/lv) rats indicated that at least one more genetic factor was responsible for Type 1 diabetes. In this study, we generated F2N2 progeny in a cross between non-diabetic F2(DR)lyp/lyp,u/u) X F344)(lyp/lyp,u/u) and diabetic DR(lyp/lyp,u/u) rats. In a subsequent total genome scan, a third factor was mapped to the 21.3-cM region on Chr 2 between D2Mit14 and D2Mit15 (peak LOD score 4.7 with 67% penetrance). Interestingly, the homozygosity of the BB allele (b/b) for the Chr 2 region was significantly associated with a greater weight reduction after fasting than the homozygosity of the F344 allele (f/f, p < 0.008). In conclusion, the development of Type I diabetes in the congenic DR(lyp/lyp) rat is controlled by at least three genes: lymphopenia, MHC, and a third factor that may play a role in metabolism and body weight regulation.
(Less)
- author
- Klaff, Lindy S. ; Koike, George ; Jiang, Jianjie ; Wang, Yanling ; Bieg, Sabine ; Pettersson, Anna ; Lander, Eric ; Jacob, Howard and Lernmark, Ake LU
- publishing date
- 1999-09-30
- type
- Contribution to journal
- publication status
- published
- in
- Mammalian Genome
- volume
- 10
- issue
- 9
- pages
- 883 - 887
- publisher
- Springer
- external identifiers
-
- scopus:0032878618
- pmid:10441739
- ISSN
- 0938-8990
- DOI
- 10.1007/s003359901108
- language
- English
- LU publication?
- no
- id
- 7e612aa6-323f-42d0-963a-13c8f3bf9b38
- date added to LUP
- 2019-06-30 23:33:39
- date last changed
- 2024-03-13 08:05:20
@article{7e612aa6-323f-42d0-963a-13c8f3bf9b38, abstract = {{<p>The genetic etiology of Type 1 (insulin-dependent) diabetes mellitus is complicated by the apparent presence of several diabetes susceptibility genetic regions. Type I diabetes in the inbred BioBreeding (BB) rat closely resembles the human disorder and was previously shown to involve two genes: the lymphopenia (lyp) region on Chromosome (Chr) 4 and RT1(u) in the major histocompatibility complex (MHC) on Chr 20. In addition, a segregation analysis of an F<sub>2</sub> intercross between the diabetes-prone congenic BB DR(lyp/lyp,u/u) and F344(+/+,lv/lv) rats indicated that at least one more genetic factor was responsible for Type 1 diabetes. In this study, we generated F<sub>2</sub>N<sub>2</sub> progeny in a cross between non-diabetic F<sub>2</sub>(DR)lyp/lyp,u/u) X F344)(lyp/lyp,u/u) and diabetic DR(lyp/lyp,u/u) rats. In a subsequent total genome scan, a third factor was mapped to the 21.3-cM region on Chr 2 between D2Mit14 and D2Mit15 (peak LOD score 4.7 with 67% penetrance). Interestingly, the homozygosity of the BB allele (b/b) for the Chr 2 region was significantly associated with a greater weight reduction after fasting than the homozygosity of the F344 allele (f/f, p < 0.008). In conclusion, the development of Type I diabetes in the congenic DR(lyp/lyp) rat is controlled by at least three genes: lymphopenia, MHC, and a third factor that may play a role in metabolism and body weight regulation.</p>}}, author = {{Klaff, Lindy S. and Koike, George and Jiang, Jianjie and Wang, Yanling and Bieg, Sabine and Pettersson, Anna and Lander, Eric and Jacob, Howard and Lernmark, Ake}}, issn = {{0938-8990}}, language = {{eng}}, month = {{09}}, number = {{9}}, pages = {{883--887}}, publisher = {{Springer}}, series = {{Mammalian Genome}}, title = {{BB rat diabetes susceptibility and body weight regulation genes colocalize on Chromosome 2}}, url = {{http://dx.doi.org/10.1007/s003359901108}}, doi = {{10.1007/s003359901108}}, volume = {{10}}, year = {{1999}}, }