Molecular Genetics of Mammalian Glycosyltransferases 
phils adhere tightly to activated endotheUum, in- 
sinuate themselves into the endothelial cell pave- 
ment lining the blood vessel, and ultimately 
come to occupy areas outside the vascular tree. 
Neutrophil adhesion to activated endothelium 
is mediated in part by a protein known as endothe- 
lial leukocyte adhesion molecule I, or ELAM-I, 
that is found on the surface of activated endothe- 
lial cells. Structural features exhibited by ELAM-I 
suggested that it might interact with an oligosac- 
charide molecule specific to the surface of neu- 
trophils, but this hypothesis had not been con- 
firmed, nor had the nature of such molecules 
been defined. By transfecting different glycosyl- 
transferase gene segments into cultured mamma- 
lian host cells, we were able to recapitulate the 
biosynthesis of several distinct sets of cell surface 
oligosaccharide molecules. We found that one 
set allowed transfected cells to adhere to ELAM-I. 
We further demonstrated that the oligosaccha- 
ride molecules were one or more members of a 
family of oligosaccharides containing sialic acid 
and fucose and were represented by a molecule 
known as the sialyl Lewis X determinant. Subse- 
quent work by our own group and others has con- 
firmed that these and other glycosyltransferase 
genes play important regulatory roles in the bio- 
synthesis of oligosaccharides recognized by 
ELAM-I. 
Recently it has also been shown that oligosac- 
charides related or identical to the sialyl Lewis X 
determinant may function in adhesive interac- 
tions exhibited by two other cell surface pro- 
teins, called GMP-140 and Mell4/Leu8. These 
latter proteins, structurally related to ELAM-I, 
also function to mediate leukocyte-endothelial 
cell adhesion in inflammation and lymphocyte 
recirculation. 
Circumstantial evidence gathered by other in- 
vestigators suggests that oligosaccharides are im- 
portantly involved in cell adhesion during mam- 
malian embryogenesis. We are directing current 
efforts toward exploring this hypothesis and 
characterizing the genes that determine these in- 
teractions, through genetic manipulation of the 
murine genome. 
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