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BB rat diabetes susceptibility and body weight regulation genes colocalize on Chromosome 2

Klaff, Lindy S. ; Koike, George ; Jiang, Jianjie ; Wang, Yanling ; Bieg, Sabine ; Pettersson, Anna ; Lander, Eric ; Jacob, Howard and Lernmark, Ake LU orcid (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.

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author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Mammalian Genome
volume
10
issue
9
pages
883 - 887
publisher
Springer
external identifiers
  • pmid:10441739
  • scopus:0032878618
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 &lt; 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}},
}