CMP-Neu5Ac Hydroxylase Null Mice as a Model for Studying Metabolic Disorders Caused by the Evolutionary Loss of Neu5Gc in Humans

Biomed Res Int. 2015;2015:830315. doi: 10.1155/2015/830315. Epub 2015 Oct 19.


The purpose of this study was to identify the modification/turnover of gene products that are altered in humans due to evolutionary loss of Neu5Gc. CMP-Neu5Ac hydroxylase- (Cmah-) deficient mice show the infiltration of Kupffer cells within liver sinusoids, whereas body and liver weight develop normally. Pathway analysis by use of Illumina MouseRef-8 v2 Expression BeadChip provided evidence that a number of biological pathways, including the glycolysis, gluconeogenesis, TCA cycle, and pentose phosphate pathways, as well as glycogen metabolism-related gene expression, were significantly upregulated in Cmah-null mice. The intracellular glucose supply in Cmah-null mice resulted in mitochondrial dysfunction, oxidative stress, and the advanced glycation end products accumulation that could further induce oxidative stress. Finally, low sirtuin-1 and sirtuin-3 gene expressions due to higher NADH/NAD in Cmah-null mice decreased Foxo-1 and MnSOD gene expression, suggesting that oxidative stress may result in mitochondrial dysfunction in Cmah-null mouse. The present study suggests that mice with CMAH deficiency can be taken as an important model for studying metabolic disorders in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cluster Analysis
  • Disease Models, Animal
  • Evolution, Molecular
  • Gene Regulatory Networks / genetics
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria, Liver / genetics*
  • Mitochondria, Liver / metabolism*
  • Mixed Function Oxygenases / deficiency*
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • Neuraminic Acids / metabolism*
  • Oxidative Stress / genetics


  • Neuraminic Acids
  • N-glycolylneuraminic acid
  • Mixed Function Oxygenases
  • CMPacetylneuraminate monooxygenase