The mouse Kell blood group gene (Kel): cDNA sequence, genomic organization, expression, and enzymatic function

The human Kell blood group system is important in transfusion medicine, sin ce Kell is a polymorphic protein and some of its antigens can cause severe reactions if mismatched blood is transfused, while maternal alloimmunizatio n may lead to fetal and neonatal anemia. In humans, Kell is an M-r 93,000 t ype II membrane glycoprotein with endothelin-3-converting enzyme activity t hat is linked by a single disulfide bond to another protein, XK, that spans the membrane ten times. An absence of XK leads to clinical symptoms termed the McLeod syndrome. We determined the cDNA sequence of the mouse Kell hom ologue, the organization of the gene, expression of the protein and its enz ymatic function on red cells. Comparison of human and mouse Kell cDNA showe d 80% nucleotide and 74% amino acid sequence identity. Notable differences are that the mouse Kell protein has eight probable N-linked carbohydrate si de chains, compared to five for human Kell, and that the mouse homologue ha s one more extracellular cysteine than human Kell protein. The mouse Kell g ene (Kel), like its human counterpart, is similarly organized into 19 exons . Kel was located to proximal Chromosome 6. Northern blot analysis showed h igh expression in spleen and weaker levels in testis and heart. Western blo t analysis of red cell membrane proteins demonstrated that mouse Kell glyco protein has an apparent M-r of 110,000 and, on removal of N-linked sugars, 80,000. As in human red cells, Kell is disulfide-linked to XK and mouse red cells have endothelin-3-converting enzyme activity.