Murine Equivalent of the Human Histo-blood Group ABO Gene Is acis-AB Gene and Encodes a Glycosyltransferase with Both A and B Transferase Activity

Abstract

We have cloned murine genomic and complementary DNA that is equivalent to the human ABO gene. The murine gene consists of at least six coding exons and spans at least 11 kilobase pairs. Exon-intron boundaries are similar to those of the human gene. Unlike human A and B genes that encode two distinct glycosyltransferases with different donor nucleotide-sugar specificities, the murine gene is a cis-AB gene that encodes an enzyme with both A and B transferase activities, and this cis-AB gene prevails in the mouse population. Cloning of the murine AB gene may be helpful in establishing a mouse model system to assess the functionality of the ABO genes in the future.Histo-blood group A/B antigens are clinically important antigens in blood transfusion and organ transplantation. These antigens are oligosaccharide antigens whose immunodominant structures are defined as GalNAc ␣133 (Fuc ␣132) Gal-and Gal ␣133 (Fuc ␣132) Gal-for A and B antigen, respectively. Functional alleles at the ABO locus encode enzymes that catalyze the final step of synthesis. A alleles encode for A transferase, which transfers the GalNAc residues from the UDPGalNAc nucleotide-sugar to the galactose residue of the acceptor H substrates defined by Fuc ␣132 Gal-. B alleles encode for B transferase that transfers the galactose residue from UDP-galactose to the same H substrates. O alleles are nonfunctional, null alleles. During the past decade, we have been studying the molecular genetic basis of the histo-blood group ABO system (1). From a human gastric carcinoma cell line cDNA library, we were able to clone human A transferase cDNA (2) based on the partial amino acid sequence of the soluble form of A transferase purified from human lung (3). Using cross-hybridization with A transferase cDNA probes, we then cloned B transferase cDNA and nonfunctional O allelic cDNA from cDNA libraries made with RNA from colon adenocarcinoma cell lines that exhibited different ABO phenotypes (4). Possible allele-specific mutations were identified. Four amino acid substitutions were discovered between A and B transferases. O alleles were more homologous to A alleles than to B alleles. A single base deletion was found near the N terminus of the coding sequence in most of the O alleles, which caused the codon frame to shift. This resulted in a truncated protein without glycosyltransferase activity. In addition to the three major alleles (A

Regulation of Glycan Structures in Animal Tissues

“…4, high in testis, base-line levels in kidney, liver, and brain) and EST abundance data (only detected in bladder, epididymus, prostate, testis, and intestine). These transcript data are consistent with the absence of detectable A/B antigens in murine blood cells and salivary secretions based on agglutination tests and immunologic detection methods (74).…”

“…The murine gene responsible for A/B histo-blood group antigen biosynthesis is a cis-AB glycosyltransferase (Abo) that can synthesize both ␣1,3GalNAc (blood group A) and ␣1,3Gal (blood group B) linkages (74). Humans synthesize A/B antigens broadly in the epithelial cells of gastrointestinal, esophageal, bronchopulmonary, oral, and urogenital tissues and bone marrow progenitors in contrast to low expression in liver, spleen, and kidney and no detectable expression in brain and muscle (57).…”

Rat Encodes the Paralogous Gene Equivalent of the Human Histo-blood Group ABO Gene

“…Used primer sequences were chosen from the fragments highly conserved between human and mouse (17). The PCR product was subcloned into a plasmid and the individual clones were sequenced.…”

“…Therefore, the low transcript level of rat B-transferase may be the main reason for the deletion of B-antigen in wild Wistar rats. Another possible reason is competition for the substrate of UDP-galactose with ␣1,3-galactosyltransferase, which was discussed in a mouse homologue with cis-AB activity (17).…”

Mosaic genealogy of the Mus musculus genome revealed by 21 nuclear genes from its three subspecies

“…Takahashi et al (2004) analyzed these sequences and detected a positive correlation between the recombination rate and nucleotide diversity within subspecies, and a negative correlation between that and G ST . The same set of nine strains was also used for the ABO blood group gene studied by Yamamoto et al (2001). We constructed phylogenetic network for each nuclear DNA locus, as well as a phylogenetic tree of concatenated sequences.…”