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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

Hawkins, T; Fuller, J; Olson, K; Speros, S and Lernmark, Åke LU (2005) In Journal of Autoimmunity 25(4). p.251-257
Abstract
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... (More)
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. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
BB rat, Lymphopenia, Gimap, Diabetes, Bone marrow transplantation
in
Journal of Autoimmunity
volume
25
issue
4
pages
251 - 257
publisher
Elsevier
external identifiers
  • scopus:27844588475
ISSN
0896-8411
DOI
10.1016/j.jaut.2005.06.003
language
English
LU publication?
no
id
e7765070-e615-4872-af1a-680c8e95596f (old id 1133065)
date added to LUP
2008-06-25 14:35:20
date last changed
2017-08-13 03:46:14
@article{e7765070-e615-4872-af1a-680c8e95596f,
  abstract     = {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.<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
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.},
  author       = {Hawkins, T and Fuller, J and Olson, K and Speros, S and Lernmark, Åke},
  issn         = {0896-8411},
  keyword      = {BB rat,Lymphopenia,Gimap,Diabetes,Bone marrow transplantation},
  language     = {eng},
  number       = {4},
  pages        = {251--257},
  publisher    = {Elsevier},
  series       = {Journal of Autoimmunity},
  title        = {DR.lyp/lyp bone marrow maintains lymphopenia and promotes diabetes in lyp/lyp but not in +/+ recipient DR.lyp BB rats},
  url          = {http://dx.doi.org/10.1016/j.jaut.2005.06.003},
  volume       = {25},
  year         = {2005},
}