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Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5. Blood 2008 Dec 15;112(13):4905-14

Date

09/18/2008

Pubmed ID

18796632

Pubmed Central ID

PMC2597598

DOI

10.1182/blood-2008-03-146555

Scopus ID

2-s2.0-58149376483   43 Citations

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 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.

Author List

Schulteis RD, Chu H, Dai X, Chen Y, Edwards B, Haribhai D, Williams CB, Malarkannan S, Hessner MJ, Glisic-Milosavljevic S, Jana S, Kerschen EJ, Ghosh S, Wang D, Kwitek AE, Lernmark A, Gorski J, Weiler H

Authors

Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin
Anne E. Kwitek PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of Wisconsin
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Hartmut Weiler PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Differentiation
Cell Survival
GTP Phosphohydrolases
GTP-Binding Proteins
Liver Failure
Mice
Mice, Mutant Strains
Natural Killer T-Cells
T-Lymphocytes
jenkins-FCD Prod-405 0f9a74600e4e79798f8fa6f545ea115f3dd948b2