Organization of the Human LU Gene and Molecular Basis of the Lu/Lu Blood Group Polymorphism

The Lutheran (Lu) blood group antigens and the B-cell adhebut includes several potential binding sites for the ubiquitous Sp1 transcription factor. In addition, the distal 5* region, sion molecule (B-CAM) epithelial cancer antigen are carried by recently cloned integral glycoproteins that belong to the encompassing nucleotidesÏ673 toÏ764, contains clustered binding sequences for the GATA, CACCC, and Ets transcripIg superfamily. We have previously shown that the Lu and B-CAM antigens are encoded by the same gene, LU, and tion factors. Analysis of the coding sequences amplified from genomic DNA of Lu(a " bÏ) or Lu(a Ï b") donors showed that alternative splicing of the primary transcript most likely accounts for the presence of both antigens on two isoforms a single nucleotide change in exon 3 (A229G) that correlates with an Aci I restriction site polymorphism and results in a that differ by the length of their cytoplasmic tails. In the present report, we isolated the human LU gene by cloning His77Arg amino-acid substitution. Polymerase chain reaction/restriction fragment length polymorphism analysis ina 20-kb HindIII fragment from Lu(a Ï b") genomic DNA. The LU gene is organized into 15 exons distributed over 12.5 kb. dicated that the A229G mutation is associated with the Lu/ Lu blood group polymorphism. When expressed in Chinese Alternative splicing of intron 13 generates the 2.5and 4.0kb transcript spliceoforms encoding the long tail and the hamster ovary (CHO) cells, Lu cDNAs carrying the A229 or the G229 produced cell surface proteins that reacted with short tail Lu polypeptides, respectively. Sequencing of the major mRNA species (2.5 kb) amplified from human bone anti-Lu or anti-Lu antibodies, respectively, showing that these nucleotides specify the Lu and Lu alleles of the Lumarrow, kidney, placenta, and skeletal muscle did not suggest the presence of tissue-specific Lu glycoprotein isotheran blood group locus. CHO cells expressing recombinant short-tail or long-tail Lu glycoproteins reacted as well with forms. The same transcription initiation point, located 22 bp upstream from the initiation codon, was characterized in anti-Lu as with anti–B-CAM antibodies, providing the definitive proof that the Lu blood group and B-CAM antigens are several tissues. In agreement with the wide tissue distribution of the Lu messengers, the GC-rich proximal 5* flanking carried by the same molecules. q 1997 by The American Society of Hematology. region of the LU gene does not contain TATA or CAAT boxes,