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 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 (mCD43) expression in the B-cell lineage where it is tightly regulated, by expressing it in peripheral B cells where it is normally absent. To drive expression of leukosialin in mature B cells, the immunoglobulin heavy chain enhancer was fused to the mCD43 gene. mCD43-immunoglobulin heavy chain enhancer transgenic mice display splenomegaly due to increased numbers of B cells. Transgenic B cells show a striking increase in their ability to survive in vitro compared to B cells from nontransgenic control mice. This prolonged survival is reflected in a decreased susceptibility to apoptosis. These observations suggest that mCD43 plays an important role in the regulation of B-cell survival. The alteration of the temporal expression, or "disregulation," of a gene in transgenic mice provides a general strategy for elucidating the in vivo role of other molecules involved in cell signaling and adhesion.
Dragone
L L
LL
Department of Microbiology and Immunology, University of Rochester Medical Center, NY 14642.
Barth
R K
RK
Sitar
K L
KL
Disbrow
G L
GL
Frelinger
J G
JG
D000818:Animals; D015703:Antigens, CD; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D002452:Cell Count; D002454:Cell Differentiation; D002470:Cell Survival; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D051917:Leukosialin; D051379:Mice; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology / Q000276:immunology*
D015703:Antigens, CD; D051917:Leukosialin; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; C497863:Spn protein, mouse