DISREGULATION OF LEUKOSIALIN (CD43, LY48, SIALOPHORIN) EXPRESSION IN THE B-CELL LINEAGE OF TRANSGENIC MICE INCREASES SPLENIC B-CELL NUMBER AND SURVIVAL

Leukosialin (also known as Ly48, CD43, and sialophorin) is a major cel l surface sialoglycoprotein found on a variety of hematopoietically de rived cells, The precise function of this molecule is poorly understoo d but it has been implicated in cell proliferation and intercellular a dhesion, We developed a transgenic mouse model to assess leukosialin's function in vivo. Our approach was to alter mouse CD43 (mCD43) expres sion in the B-cell lineage where it is tightly regulated, by expressin g it in peripheral B cells where it is normally absent, To drive expre ssion of leukosialin in mature B cells, the immunoglobulin heavy chain enhancer was fused to the mCD43 gene, mCD43-immunoglobulin heavy chai n enhancer transgenic mice display splenomegaly due to increased numbe rs of B cells, Transgenic B cells show a striking increase in their ab ility to survive in vitro compared to B cells from nontransgenic contr ol mice. This prolonged survival is reflected in a decreased susceptib ility to apoptosis. These observations suggest that mCD43 plays an imp ortant role in the regulation of B-cell survival, The alteration of th e temporal expression, or ''disregulation,'' of a gene in transgenic m ice provides a general strategy for elucidating the in vivo role of ot her molecules involved in cell signaling and adhesion.