Molecular Characterization of the Cytidine Monophosphate-N-Acetylneuraminic Acid Hydroxylase (CMAH) Gene Associated With the Feline AB Blood Group System

PLoS One. 2016 Oct 18;11(10):e0165000. doi: 10.1371/journal.pone.0165000. eCollection 2016.


Cat's AB blood group system (blood types A, B, and AB) is of major importance in feline transfusion medicine. Type A and type B antigens are Neu5Gc and Neu5Ac, respectively, and the enzyme CMAH participating in the synthesis of Neu5Gc from Neu5Ac is associated with this cat blood group system. Rare type AB erythrocytes express both Neu5Gc and Neu5Ac. Cat serum contains naturally occurring antibodies against antigens occurring in the other blood types. To understand the molecular genetic basis of this blood group system, we investigated the distribution of AB blood group antigens, CMAH gene structure, mutation, diplotypes, and haplotypes of the cat CMAH genes. Blood-typing revealed that 734 of the cats analyzed type A (95.1%), 38 cats were type B (4.9%), and none were type AB. A family of three Ragdoll cats including two type AB cats and one type A was also used in this study. CMAH sequence analyses showed that the CMAH protein was generated from two mRNA isoforms differing in exon 1. Analyses of the nucleotide sequences of the 16 exons including the coding region of CMAH examined in the 34 type B cats and in the family of type AB cats carried the CMAH variants, and revealed multiple novel diplotypes comprising several polymorphisms. Haplotype inference, which was focused on non-synonymous SNPs revealed that eight haplotypes carried one to four mutations in CMAH, and all cats with type B (n = 34) and AB (n = 2) blood carried two alleles derived from the mutated CMAH gene. These results suggested that double haploids selected from multiple recessive alleles in the cat CMAH loci were highly associated with the expression of the Neu5Ac on erythrocyte membrane in types B and AB of the feline AB blood group system.

MeSH terms

  • Alleles
  • Animals
  • Blood Group Antigens / genetics
  • Blood Group Antigens / immunology
  • Blood Group Antigens / metabolism*
  • Cats
  • Erythrocytes / metabolism
  • Exons
  • Genetic Loci
  • Haplotypes
  • Mixed Function Oxygenases / chemistry
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • N-Acetylneuraminic Acid / metabolism
  • Neuraminic Acids / metabolism
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA


  • Blood Group Antigens
  • Neuraminic Acids
  • RNA, Messenger
  • N-glycolylneuraminic acid
  • Mixed Function Oxygenases
  • CMPacetylneuraminate monooxygenase
  • N-Acetylneuraminic Acid

Grant support

This work was supported by JSPS KAKENHI Grant Numbers 25450454 and 16K08062.