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BB rat Gimap gene expression in sorted lymphoid T and B cells

Author:
  • Daniel H. Moralejo
  • Jessica Fuller
  • Elizabeth A. Rutledge
  • Brian Van Yserloo
  • Ruth A. Ettinger
  • Richard Jensen
  • William Osborne
  • Anne Kwitek
  • Åke Lernmark
Publishing year: 2011
Language: English
Pages: 748-754
Publication/Series: Life Sciences
Volume: 89
Issue: 19-20
Document type: Journal article
Publisher: Elsevier

Abstract english

Aims: The Gimap gene family has been shown to be integral to T cell survival and development. A frameshift mutation in Gimap5, one of seven members of the Gimap family, results in lymphopenia and is a prerequisite for spontaneous type 1 diabetes (T1D) in the BioBreeding (BB) rat. While not contributing to lymphopenia, the Gimap family members proximal to Gimap5, encompassed within the Iddm39 quantitative trait locus (QTL), have been implicated in T1D. We hypothesized that expression of the Gimap family members within the Iddm39 QTL, during thymocyte development as well as in peripheral T and B cells contribute to T1D. Main methods: Cell sorted subpopulations were analyzed by quantitative real time (qRT) PCR. Key findings: Gimap4 expression was reduced in DR.(lyp/lyp) rat double negative, double positive and CD8 single positive (SP) thymocytes while expression of Gimap8, Gimap6, and Gimap7 was reduced only in CD8 SP thymocytes. Interestingly, expression of the entire Gimap gene family was reduced in DR.(lyp/lyp) rat peripheral T cells compared to non-lymphopenic, non-diabetic DR.(+/+) rats. With the exception of Gimap6. the Gimap family genes were not expressed in B cells from spleen and mesenteric lymph node (MLN). Expression of Gimap9 was only detected in hematopoietic cells of non B cell lineage such as macrophage, dendritic or NK cells. Significance: These results suggest that lack of the Gimap5 protein in the DR.(lyp/lyp) congenic rat was associated with impaired expression of the entire family of Gimap genes and may regulate T cell homeostasis in the peripheral lymphoid organs. (C) 2011 Elsevier Inc. All rights reserved.

Keywords

  • Endocrinology and Diabetes
  • Gimap
  • Lymphopenia
  • Autoimmunity
  • Type 1 diabetes

Other

Published
  • Diabetes and Celiac Unit
  • ISSN: 1879-0631
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

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+46 70 616 47 79

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Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00