Molecular cloning, chromosomal assignment and tissue-specific expression of a murine α(1,2)fucosyltransferase expressed in thymic and epididymal epithelial cells

摘要

pTerminal Fucα(1-2)Galβ epitopes have been proposed to play significant roles in cell–cell interactions in development, cell adhesion, and malignant transformation. To begin to investigate the regulation and function of α(1-2)fucosylated epitopes in an animal model, we have isolated and characterized a mouse genomic DNA segment encoding a protein orthologous to the human iH/i blood group locus α(1,2)fucosyltransferase (FUT1). This segment maintains an open reading frame encoding 376 amino acids sharing 75% sequence identity with the enzyme encoded by human FUT1, and 55% sequence identity with the enzyme encoded by the human iSecretor/i blood group locus (FUT2). Expression of the open reading frame in COS-7 cells yields an α(1,2)fucosyltransferase activity with a iK/isubm/sub of 7.6 mM for phenyl-β-d-galactoside. Southern blotting and interspecific backcross analyses indicate that this murine locus represents a single copy sequence mapping to a novel locus 2.1 centimorgans from the iKlk/i1 locus, in a region of homology between mouse chromosome 7 and the human FUT1 locus on the long arm of chromosome 19. Mouse FUT1 yields a 2.8 kb mRNA transcript identifiable in many organs, including thymus, lung, stomach, pancreas, small intestine, colon, uterus and epididymis. Hybridization analyses iin situ/i localize expression of FUT1 transcripts to thymic medullary and epididymal epithelial cells, implying that this gene determines the expression of cell surface Fucα(1-2)Galβ epitopes in these tissues./p