ABSTRACT
In domestic cats, the AB blood group system consists of the three types A, B, and C (usually called AB), which vary in frequency among breeds and geographic regions. Mismatches cause acute hemolytic transfusion reactions and hemolysis of the newborn due to the presence of naturally occurring anti-A alloantibodies. Cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) converts N-acetylneuraminic acid (type B) to N-glycolylneuraminic acid (type A), and type C erythrocytes express both antigens. We examined the feline CMAH coding regions and genotyped cats to characterize type A, B, and C animals. Of 421 phenotypically typed cats, 60% were A, 35% B and 5% C. Among the 70 cats for which the CMAH coding region was sequenced, 13 new variants were identified in addition to 16 of the previously reported 18 variants. The CMAH variant c.268T>A is seen in type B cats of most breeds, and the variant c.179G>T results in type B in Turkish breeds. The variants c.1322delT and c.933delA cause frameshifts with early stop codons and thereby type B in some Ragdolls and domestic shorthair cats, respectively. Protein modeling with PROVEAN affirmed their deleterious effects. No type A and C cats had more than one allele with one of the above variants. Variant analysis of three SNVs (c.142G>A, c.268T>A and Δ-53) and blood typing of an additional 351 typed cats showed complete phenotype-genotype concordance. In conclusion, the three CMAH variants c.179G>T, c.268T>A and c.1322delT are the main reasons for the defective NeuGc synthesis causing blood type B in domestic purebred and non-pedigreed cats. Together with the variant c.364C>T for type C in Ragdolls they offer a molecular screening scheme for clinical diagnostics to assure blood type compatibility.
Subject(s)
Animals, Domestic/classification , Blood Group Antigens/genetics , Genotyping Techniques/veterinary , Mixed Function Oxygenases/genetics , Point Mutation , Animals , Animals, Domestic/genetics , Breeding , Cats , Exons , Frameshift Mutation , N-Acetylneuraminic Acid/metabolism , Neuraminic Acids/metabolism , Sequence Analysis, DNA/veterinaryABSTRACT
Dichloroacetate (DCA) and trichloroacetate (TCA) are drinking-water chlorination by-products previously found to induce oxidative stress (OS) in hepatic tissues of B6C3F1 male mice. To assess the effects of mixtures of the compounds on OS, groups of male B6C3F1 mice were treated daily by gavage with DCA at doses of 7.5, 15, or 30 mg/kg/d, TCA at doses of 12.5, 25, or 50 mg/kg/d, and 3 mixtures of DCA and TCA (Mix I, Mix II, and Mix III), for 13 wk. The concentrations of the compounds in Mix I, Mix II, and Mix III corresponded to those producing approximately 15, 25, and 35%, respectively, of maximal induction of OS by individual compounds. Livers were assayed for production of superoxide anion (SA), lipid peroxidation (LP), and DNA single-strand breaks (SSB). DCA, TCA, and the mixtures produced dose-dependent increases in the three tested biomarkers. Mix I and II effects on the three biomarkers, and Mix III effect on SA production were found to be additive, while Mix III effects on LP and DNA-SSB were shown to be greater than additive. Induction of OS in livers of B6C3F1 mice after subchronic exposure to DCA and TCA was previously suggested as an important mechanism in chronic hepatotoxicity/hepatocarcinogenicity induced by these compounds. Hence, there may be rise in exposure risk to these compounds as these agents coexist in drinking water.
