Mice lacking the orphan G protein-coupled receptor G2A develop a late-onset autoimmune syndrome.
Mice with a targeted disruption of the gene encoding a lymphoid-expressed orphan G protein-coupled receptor, G2A, demonstrate a normal pattern of T and B lineage differentiation through young adulthood. As G2A-deficient animals age, they develop secondary lymphoid organ enlargement associated with abnormal expansion of both T and B lymphocytes. Older G2A-deficient mice (>1 year) develop a slowly progressive wasting syndrome, characterized by lymphocytic infiltration into various tissues, glomerular immune complex deposition, and anti-nuclear autoantibodies. G2A-deficient T cells are hyperresponsive to TCR stimulation, exhibiting enhanced proliferation and a lower threshold for activation. Our findings demonstrate that G2A plays a critical role in controlling peripheral lymphocyte homeostasis and that its ablation results in the development of a novel, late-onset autoimmune syndrome.
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L Q
LQ
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kabarowski
J H
JH
Weng
Z
Z
Satterthwaite
A B
AB
Harvill
E T
ET
Jensen
E R
ER
Miller
J F
JF
Witte
O N
ON
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000276:immunology*; D002455:Cell Division; D005260:Female; D019204:GTP-Binding Proteins; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D043562:Receptors, G-Protein-Coupled; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D018797:Cell Cycle Proteins; C115270:G2A receptor; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins