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Sequence Variation and Expression of the Gimap Gene Family in the BB Rat

Rutledge, Elizabeth A.; Fuller, Jessica LU ; Van Yserloo, Brian; Moralejo, Daniel H.; Ettinger, Ruth A.; Gaur, Prashant; Hoehna, Jana L.; Peterson, Morgan R.; Jensen, Richard and Kwitek, Anne E., et al. (2009) In Experimental Diabetes Research
Abstract
Positional cloning of lymphopenia (lyp) in the BB rat revealed a frameshift mutation in Gimap5, a member of at least seven related GTPase Immune Associated Protein genes located on rat chromosome 4q24. Our aim was to clone and sequence the cDNA of the BB diabetes prone (DP) and diabetes resistant (DR) alleles of all seven Gimap genes in the congenic DR.lyp rat line with 2 Mb of BB DP DNA introgressed onto the DR genetic background. All (100%) DR.(lyp/lyp) rats are lymphopenic and develop type 1 diabetes (T1D) by 84 days of age while DR.(+/+) rats remain T1D and lyp resistant. Among the seven Gimap genes, the Gimap5 frameshift mutation, a mutant allele that produces no protein, had the greatest impact on lymphopenia in the DR.(lyp/lyp) rat.... (More)
Positional cloning of lymphopenia (lyp) in the BB rat revealed a frameshift mutation in Gimap5, a member of at least seven related GTPase Immune Associated Protein genes located on rat chromosome 4q24. Our aim was to clone and sequence the cDNA of the BB diabetes prone (DP) and diabetes resistant (DR) alleles of all seven Gimap genes in the congenic DR.lyp rat line with 2 Mb of BB DP DNA introgressed onto the DR genetic background. All (100%) DR.(lyp/lyp) rats are lymphopenic and develop type 1 diabetes (T1D) by 84 days of age while DR.(+/+) rats remain T1D and lyp resistant. Among the seven Gimap genes, the Gimap5 frameshift mutation, a mutant allele that produces no protein, had the greatest impact on lymphopenia in the DR.(lyp/lyp) rat. Gimap4 and Gimap1 each had one amino acid substitution of unlikely significance for lymphopenia. Quantitative RT-PCR analysis showed a reduction in expression of all seven Gimap genes in DR.lyp/lyp spleen and mesenteric lymph nodes when compared to DR.+/+. Only four; Gimap1, Gimap4, Gimap5, and Gimap9 were reduced in thymus. Our data substantiates the Gimap5 frameshift mutation as the primary defect with only limited contributions to lymphopenia from the remaining Gimap genes. Copyright (C) 2009 Elizabeth A. Rutledge et al. (Less)
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Experimental Diabetes Research
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Hindawi Publishing Corporation
external identifiers
  • wos:000267262200001
  • scopus:67650322087
ISSN
1687-5214
DOI
10.1155/2009/835650
language
English
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yes
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d894609c-9f75-4ff3-b661-8f3d0664db28 (old id 1441414)
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2009-07-28 09:10:13
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@article{d894609c-9f75-4ff3-b661-8f3d0664db28,
  abstract     = {Positional cloning of lymphopenia (lyp) in the BB rat revealed a frameshift mutation in Gimap5, a member of at least seven related GTPase Immune Associated Protein genes located on rat chromosome 4q24. Our aim was to clone and sequence the cDNA of the BB diabetes prone (DP) and diabetes resistant (DR) alleles of all seven Gimap genes in the congenic DR.lyp rat line with 2 Mb of BB DP DNA introgressed onto the DR genetic background. All (100%) DR.(lyp/lyp) rats are lymphopenic and develop type 1 diabetes (T1D) by 84 days of age while DR.(+/+) rats remain T1D and lyp resistant. Among the seven Gimap genes, the Gimap5 frameshift mutation, a mutant allele that produces no protein, had the greatest impact on lymphopenia in the DR.(lyp/lyp) rat. Gimap4 and Gimap1 each had one amino acid substitution of unlikely significance for lymphopenia. Quantitative RT-PCR analysis showed a reduction in expression of all seven Gimap genes in DR.lyp/lyp spleen and mesenteric lymph nodes when compared to DR.+/+. Only four; Gimap1, Gimap4, Gimap5, and Gimap9 were reduced in thymus. Our data substantiates the Gimap5 frameshift mutation as the primary defect with only limited contributions to lymphopenia from the remaining Gimap genes. Copyright (C) 2009 Elizabeth A. Rutledge et al.},
  articleno    = {835650},
  author       = {Rutledge, Elizabeth A. and Fuller, Jessica and Van Yserloo, Brian and Moralejo, Daniel H. and Ettinger, Ruth A. and Gaur, Prashant and Hoehna, Jana L. and Peterson, Morgan R. and Jensen, Richard and Kwitek, Anne E. and Lernmark, Åke},
  issn         = {1687-5214},
  language     = {eng},
  publisher    = {Hindawi Publishing Corporation},
  series       = {Experimental Diabetes Research},
  title        = {Sequence Variation and Expression of the Gimap Gene Family in the BB Rat},
  url          = {http://dx.doi.org/10.1155/2009/835650},
  year         = {2009},
}