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Introgression of F344 rat genomic DNA on BB rat chromosome 4 generates diabetes-resistant lymphopenic BB rats.

Fuller, J M; Kwitek, A E; Hawkins, T J; Moralejo, D H; Lu, W; Tupling, T D; Macmurray, A J; Borchardt, G; Hasinoff, M and Lernmark, Åke LU (2006) In Diabetes 55. p.3351-3357
Abstract
Failure to express the Gimap5 protein is associated with lymphopenia (lyp) and linked to spontaneous diabetes in the diabetes-prone BioBreeding (BBDP) rat. Gimap5 is a member of seven related genes located within 150 Kb on rat chromosome 4. Congenic DR.lyp/lyp rats, where BBDP lyp was introgressed onto the diabetes-resistant BBDR background (BBDR.BBDP.lyp/lyp), all develop diabetes between 46 and 81 days of age (mean ± SE, 61 ± 1), whereas DR.lyp/+ and DR.+/+ rats are nonlymphopenic and diabetes resistant. In an intercross between F1(BBDP x F344) rats, we identified a rat with a recombination event on chromosome 4, allowing us to fix 33 Mb of F344 between D4Rat253 and D4Rhw6 in the congenic DR.lyp rat line. Gimap1 and Gimap5 were the only... (More)
Failure to express the Gimap5 protein is associated with lymphopenia (lyp) and linked to spontaneous diabetes in the diabetes-prone BioBreeding (BBDP) rat. Gimap5 is a member of seven related genes located within 150 Kb on rat chromosome 4. Congenic DR.lyp/lyp rats, where BBDP lyp was introgressed onto the diabetes-resistant BBDR background (BBDR.BBDP.lyp/lyp), all develop diabetes between 46 and 81 days of age (mean ± SE, 61 ± 1), whereas DR.lyp/+ and DR.+/+ rats are nonlymphopenic and diabetes resistant. In an intercross between F1(BBDP x F344) rats, we identified a rat with a recombination event on chromosome 4, allowing us to fix 33 Mb of F344 between D4Rat253 and D4Rhw6 in the congenic DR.lyp rat line. Gimap1 and Gimap5 were the only members of the Gimap family remaining homozygous for the BBDP allele. Offspring homozygous for the F344 allele (f/f) between D4Rat253 and D4Rhw6 were lymphopenic (85 of 85, 100%) but did not develop diabetes (0 of 85). During rescue of the recombination, 102 of 163 (63%) rats heterozygous (b/f) for the recombination developed diabetes between 52 and 222 days of age (88 ± 3). Our data demonstrate that introgression of a 33-Mb region of the F344 genome, proximal to the mutated Gimap5 gene, renders the rat diabetes resistant despite being lymphopenic. Spontaneous diabetes in the BB rat may therefore be controlled, in part, by a diabetogenic factor(s), perhaps unrelated to the Gimap5 mutation on rat chromosome 4. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
55
pages
3351 - 3357
publisher
American Diabetes Association
external identifiers
  • scopus:33845515727
ISSN
1939-327X
DOI
10.2337/db06-0715
language
English
LU publication?
yes
id
a2fdf92b-b80a-472b-b25c-861a9105c3ac (old id 1136253)
date added to LUP
2008-06-11 15:24:22
date last changed
2017-02-26 04:31:07
@article{a2fdf92b-b80a-472b-b25c-861a9105c3ac,
  abstract     = {Failure to express the Gimap5 protein is associated with lymphopenia (lyp) and linked to spontaneous diabetes in the diabetes-prone BioBreeding (BBDP) rat. Gimap5 is a member of seven related genes located within 150 Kb on rat chromosome 4. Congenic DR.lyp/lyp rats, where BBDP lyp was introgressed onto the diabetes-resistant BBDR background (BBDR.BBDP.lyp/lyp), all develop diabetes between 46 and 81 days of age (mean ± SE, 61 ± 1), whereas DR.lyp/+ and DR.+/+ rats are nonlymphopenic and diabetes resistant. In an intercross between F1(BBDP x F344) rats, we identified a rat with a recombination event on chromosome 4, allowing us to fix 33 Mb of F344 between D4Rat253 and D4Rhw6 in the congenic DR.lyp rat line. Gimap1 and Gimap5 were the only members of the Gimap family remaining homozygous for the BBDP allele. Offspring homozygous for the F344 allele (f/f) between D4Rat253 and D4Rhw6 were lymphopenic (85 of 85, 100%) but did not develop diabetes (0 of 85). During rescue of the recombination, 102 of 163 (63%) rats heterozygous (b/f) for the recombination developed diabetes between 52 and 222 days of age (88 ± 3). Our data demonstrate that introgression of a 33-Mb region of the F344 genome, proximal to the mutated Gimap5 gene, renders the rat diabetes resistant despite being lymphopenic. Spontaneous diabetes in the BB rat may therefore be controlled, in part, by a diabetogenic factor(s), perhaps unrelated to the Gimap5 mutation on rat chromosome 4.},
  author       = {Fuller, J M and Kwitek, A E and Hawkins, T J and Moralejo, D H and Lu, W and Tupling, T D and Macmurray, A J and Borchardt, G and Hasinoff, M and Lernmark, Åke},
  issn         = {1939-327X},
  language     = {eng},
  pages        = {3351--3357},
  publisher    = {American Diabetes Association},
  series       = {Diabetes},
  title        = {Introgression of F344 rat genomic DNA on BB rat chromosome 4 generates diabetes-resistant lymphopenic BB rats.},
  url          = {http://dx.doi.org/10.2337/db06-0715},
  volume       = {55},
  year         = {2006},
}