Receptor Linked to an Autoimmune Disease

Abstract

The orphan G protein-coupled receptor G2A is predominantly expressed in lymphocytes and was known to regulate cell proliferation and the actin cytoskeleton. Le et al. have now knocked out G2A in mice, and the phenotype points to a role of this receptor in negatively regulating lymphocyte proliferation. The mice appeared normal early in life, but later exhibited hyperproliferation of T and B cells. Lymphoid organs were enlarged, and lymphocytes infiltrated into other organs, disrupting tissue architecture. Production of autoantibodies against nuclear antigens indicated development of a late-onset autoimmune disorder. The authors propose that G2A maintains lymphocyte growth and homeostasis. The molecular basis for the hyperproliferation has yet to be determined. L. Q. Le, J. H. S. Kabarowski, Z. Weng, A. B. Satterthwaite, E. T. Harvill, E. R. Jensen, J. F. Miller, O. N. Witte, Mice lacking the orphan G protein-coupled receptor G2A develop a late-onset autoimmune syndrome. Immunity 14 , 561-571 (2001). [Online Journal]