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Åke Lernmark

Principal investigator

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DR.lyp/lyp bone marrow maintains lymphopenia and promotes diabetes in lyp/lyp but not in +/+ recipient DR.lyp BB rats

Author

  • T Hawkins
  • J Fuller
  • K Olson
  • S Speros
  • Åke Lernmark

Summary, in English

Lymphopenia is due to a frameshift mutation in Gimap5 on rat chromosome 4 and is linked to type 1 diabetes in the diabetes prone (DP) BB rat. The hypothesis that bone marrow derived cells confer the lymphopenia phenotype was tested by reciprocal bone marrow transplantation in 40-day-old lethally irradiated diabetes resistant (DR) congenic DR.lyp/lyp (lymphopenia and diabetes) and DR.+/+ (no lymphopenia and no diabetes) rats.



In two independent series of transplants, all DR.lyp/lyp rats (n = 5 and 4) receiving DR.lyp/lyp bone marrow retained lymphopenia and developed insulitis (5/5 and 4/4) as well as diabetes in some (2/5 and 3/4). Both DR.+/+ and DR.lyp/lyp rats receiving DR.+/+ bone marrow cells as well as DR.+/+ rats receiving DR.lyp/lyp bone marrow cells showed no lymphopenia or diabetes. In accordance with earlier studies in non-congenic BB rats, the DR.+/+ rats receiving DR.lyp/lyp bone marrow cells recapitulated an intermediary phenotype rather than the +/+ or lyp/lyp phenotypes.



Our data demonstrate that BBDP rat lymphopenia and diabetes are transferred by bone marrow transplantation to syngeneic DR.lyp/lyp but not DR.+/+ recipients. The intermediary recapitulation of DR.lyp/lyp T cells in recipient DR.±/± rats suggests that radiation resistant ±/± T cells, the Gimap5 mutation in bone marrow cells, or both may not support the development of lymphopenia.

Publishing year

2005

Language

English

Pages

251-257

Publication/Series

Journal of Autoimmunity

Volume

25

Issue

4

Document type

Journal article

Publisher

Elsevier

Topic

  • Rheumatology and Autoimmunity

Keywords

  • BB rat
  • Lymphopenia
  • Gimap
  • Diabetes
  • Bone marrow transplantation

Status

Published

ISBN/ISSN/Other

  • ISSN: 0896-8411