DR.lyp/lyp bone marrow maintains lymphopenia and promotes diabetes in lyp/lyp but not in +/+ recipient DR.lyp BB rats
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1133065
- author
- Hawkins, T ; Fuller, J ; Olson, K ; Speros, S and Lernmark, Åke LU
- publishing date
- 2005
- 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
- 2016-04-01 12:29:48
- date last changed
- 2022-04-21 08:16:06
@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}}, keywords = {{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}}, doi = {{10.1016/j.jaut.2005.06.003}}, volume = {{25}}, year = {{2005}}, }