Leukosialin (also known as Ly48, CD43, and sialophorin) is a major cell surface sialoglycoprotein found on a variety of hematopoietically derived cells. The precise function of this molecule is poorly understood but it has been implicated in cell proliferation and intercellular adhesion. We developed a transgenic mouse model to assess leukosialin's function in vivo. Our approach was to alter mouse CD43 Leukosialin [also designated as CD43, sialophorin and large sialoglycoprotein in humans, Ly48 or mouse CD43 (mCD43) in mice, and W3/13 in rats] is a major cell surface sialoglycoprotein found on T cells, granulocytes, macrophages, and both erythroid and B cells at specific stages of development (1). Altered expression of this molecule has been associated with the X chromosome-linked immunodeficiency disease Wiskott-Aldrich syndrome (2-4). Further interest in CD43 has been generated by the finding that anti-CD43 antibodies are present in AIDS patients, leading to speculation that these antibodies might contribute to human immunodeficiency virus-mediated immunodeficiency (5).The reported association of CD43 with specific immunodeficiency diseases and the unusual structural features of this molecule have fueled speculations regarding its function.CD43 has an extracellular domain that is highly 0-glycosylated, with carbohydrates making up >50% of its mass, and a relatively long intracellular domain (6, 7). DNA sequence comparison of rat, human, and mouse CD43 genes reveals that the transmembrane and intracellular domains are highly conserved compared to the extracellular portion, indicating differential selective pressures on either end of this protein (6)(7)(8)(9)(10)(11)(12)