Mice lacking the orphan G protein-coupled receptor G2A develop a late-onset autoimmune syndrome

Academic Article


  • 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.
  • Published In

  • Immunity  Journal
  • Digital Object Identifier (doi)

    Author List

  • Le LQ; Kabarowski JHS; Weng Z; Satterthwaite AB; Harvill ET; Jensen ER; Miller JF; Witte ON
  • Start Page

  • 561
  • End Page

  • 571
  • Volume

  • 14
  • Issue

  • 5