Sequence Variation and Expression of the Gimap Gene Family in the BB Rat
(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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- author
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Experimental Diabetes Research
- article number
- 835650
- publisher
- Hindawi Limited
- external identifiers
-
- wos:000267262200001
- scopus:67650322087
- ISSN
- 1687-5214
- DOI
- 10.1155/2009/835650
- language
- English
- LU publication?
- yes
- id
- d894609c-9f75-4ff3-b661-8f3d0664db28 (old id 1441414)
- date added to LUP
- 2016-04-01 11:50:30
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- 2022-01-26 19:03:31
@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.}}, 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 Limited}}, 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}}, doi = {{10.1155/2009/835650}}, year = {{2009}}, }