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Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

Schulteis, Ryan D.; Chu, Haiyan; Dai, Xuezhi; Chen, Yuhong; Edwards, Brandon; Haribhai, Dipica; Williams, Calvin B.; Malarkannan, Subramaniam; Hessner, Martin J and Glisic-Milosavljevic, Sanja, et al. (2008) In Blood 112(13). p.4905-4914
Abstract

The loss of Gimap5 (GTPase of the immune-associated protein 5) gene function is the underlying cause of lymphopenia and autoimmune diabetes in the BioBreeding (BB) rat. The in vivo function of murine gimap5 is largely unknown. We show that selective gene ablation of the mouse gimap5 gene impairs the final intrathymic maturation of CD8 and CD4 T cells and compromises the survival of postthymic CD4 and CD8 cells, replicating findings in the BB rat model. In addition, gimap5 deficiency imposes a block of natural killer (NK)- and NKT-cell differentiation. Development of NK/NKT cells is restored on transfer of gimap5 -/- bone marrow into a wild-type environment. Mice lacking gimap5 have a median survival of 15 weeks, exhibit... (More)

The loss of Gimap5 (GTPase of the immune-associated protein 5) gene function is the underlying cause of lymphopenia and autoimmune diabetes in the BioBreeding (BB) rat. The in vivo function of murine gimap5 is largely unknown. We show that selective gene ablation of the mouse gimap5 gene impairs the final intrathymic maturation of CD8 and CD4 T cells and compromises the survival of postthymic CD4 and CD8 cells, replicating findings in the BB rat model. In addition, gimap5 deficiency imposes a block of natural killer (NK)- and NKT-cell differentiation. Development of NK/NKT cells is restored on transfer of gimap5 -/- bone marrow into a wild-type environment. Mice lacking gimap5 have a median survival of 15 weeks, exhibit chronic hepatic hematopoiesis, and in later stages show pronounced hepatocyte apoptosis, leading to liver failure. This pathology persists in a Rag2-deficient background in the absence of mature B, T, or NK cells and cannot be adoptively transferred by transplanting gimap5 -/- bone marrow into wild-type recipients. We conclude that mouse gimap5 is necessary for the survival of peripheral T cells, NK/NKT-cell development, and the maintenance of normal liver function. These functions involve cell-intrinsic as well as cell-extrinsic mechanisms. © 2008 by The American Society of Hematology.

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published
in
Blood
volume
112
issue
13
pages
10 pages
publisher
American Society of Hematology
external identifiers
  • scopus:58149376483
ISSN
0006-4971
DOI
10.1182/blood-2008-03-146555
language
English
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no
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30befa30-e5be-4758-b2f5-61dc6d7c98be
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2017-09-07 12:15:11
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2017-09-07 12:15:11
@article{30befa30-e5be-4758-b2f5-61dc6d7c98be,
  abstract     = {<p>The loss of Gimap5 (GTPase of the immune-associated protein 5) gene function is the underlying cause of lymphopenia and autoimmune diabetes in the BioBreeding (BB) rat. The in vivo function of murine gimap5 is largely unknown. We show that selective gene ablation of the mouse gimap5 gene impairs the final intrathymic maturation of CD8 and CD4 T cells and compromises the survival of postthymic CD4 and CD8 cells, replicating findings in the BB rat model. In addition, gimap5 deficiency imposes a block of natural killer (NK)- and NKT-cell differentiation. Development of NK/NKT cells is restored on transfer of gimap5 <sup>-/-</sup> bone marrow into a wild-type environment. Mice lacking gimap5 have a median survival of 15 weeks, exhibit chronic hepatic hematopoiesis, and in later stages show pronounced hepatocyte apoptosis, leading to liver failure. This pathology persists in a Rag2-deficient background in the absence of mature B, T, or NK cells and cannot be adoptively transferred by transplanting gimap5 <sup>-/-</sup> bone marrow into wild-type recipients. We conclude that mouse gimap5 is necessary for the survival of peripheral T cells, NK/NKT-cell development, and the maintenance of normal liver function. These functions involve cell-intrinsic as well as cell-extrinsic mechanisms. © 2008 by The American Society of Hematology.</p>},
  author       = {Schulteis, Ryan D. and Chu, Haiyan and Dai, Xuezhi and Chen, Yuhong and Edwards, Brandon and Haribhai, Dipica and Williams, Calvin B. and Malarkannan, Subramaniam and Hessner, Martin J and Glisic-Milosavljevic, Sanja and Jana, Srikanta and Kerschen, Edward J. and Ghosh, Soumitra and Wang, Demin and Kwitek, Anne E. and Lernmark, Ake and Gorski, Jack and Weiler, Hartmut},
  issn         = {0006-4971},
  language     = {eng},
  number       = {13},
  pages        = {4905--4914},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5},
  url          = {http://dx.doi.org/10.1182/blood-2008-03-146555},
  volume       = {112},
  year         = {2008},
}