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Åke Lernmark

Principal investigator

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

Author

  • Elizabeth A. Rutledge
  • Jessica Fuller
  • Brian Van Yserloo
  • Daniel H. Moralejo
  • Ruth A. Ettinger
  • Prashant Gaur
  • Jana L. Hoehna
  • Morgan R. Peterson
  • Richard Jensen
  • Anne E. Kwitek
  • Åke Lernmark

Summary, in English

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.

Department/s

  • Diabetes and Celiac Unit

Publishing year

2009

Language

English

Publication/Series

Experimental Diabetes Research

Document type

Journal article

Publisher

Hindawi Limited

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 1687-5214