The CD34 family: Proteins with related structure that play an essential role in murine development

CD34 is a cell surface sialomucin expressed by hematopoietic precursors and vascular endothelia. Despite its widespread use as a marker of early hematopoietic precursors, little is known about its function on these cells and deletion of the encoding gene in mice results in a surprisingly mild phenotype. We have now identified MEP21/PCLP-1 as a CD34-related mucin with a similar gene structure, conservation of all protein structural motifs, and an overlapping expression pattern. Interestingly, deletion of the MEP21 gene alone results in perinatal lethality due to defects in tissues that normally express MEP21 but no CD34 (kidney podocytes and the lining of the coelomic cavity). In these tissues we observe excessive adhesion suggesting that the normal function of MEP21 is to act as a “molecular Teflon” and cell block adhesion. However, hematopoietic and vascular cells in these mice are normal and we are currently generating MEP21/CD34 double deficient mice to test for functional redundancy of the molecules in these cells. Using the regions of conserved sequence homology between MEP21 and CD34 we have now identified another gene, called MEP42, that represents a third member of this family. As with MEP21 and CD34, MEP42 is expressed by all vascular endothelia and a subset of hematopoietic cells, but it has several unique biochemical features that may indicate a distinct function. MEP42 also has a more broad distribution in hematopoietic tissues (20% of bone marrow cells, 30% of thymocytes, 10% of lymph node cells) than either CD34 or MEP21. Thus, the data suggest that CD34 is the prototypic member of a family of at least three proteins that function to modulate the adhesive properties of cells.