Gene expression and pathway analysis of effects of the CMAH deactivation on mouse lung, kidney and heart

PLoS One. 2014 Sep 17;9(9):e107559. doi: 10.1371/journal.pone.0107559. eCollection 2014.


Background: N-glycolylneuraminic acid (Neu5Gc) is generated by hydroxylation of CMP-Neu5Ac to CMP-Neu5Gc, catalyzed by CMP-Neu5Ac hydroxylase (CMAH). However, humans lack this common mammalian cell surface molecule, Neu5Gc, due to inactivation of the CMAH gene during evolution. CMAH is one of several human-specific genes whose function has been lost by disruption or deletion of the coding frame. It has been suggested that CMAH inactivation has resulted in biochemical or physiological characteristics that have resulted in human-specific diseases.

Methodology/principal findings: To identify differential gene expression profiles associated with the loss of Neu5Gc expression, we performed microarray analysis using Illumina MouseRef-8 v2 Expression BeadChip, using the main tissues (lung, kidney, and heart) from control mice and CMP-Neu5Ac hydroxylase (Cmah) gene knock-out mice, respectively. Out of a total of 25,697 genes, 204, 162, and 147 genes were found to be significantly modulated in the lung, kidney, and heart tissues of the Cmah null mouse, respectively. In this study, we examined the gene expression profiles, using three commercial pathway analysis software packages: Ingenuity Pathways Analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and Pathway Studio. The gene ontology analysis revealed that the top 6 biological processes of these genes included protein metabolism and modification, signal transduction, lipid, fatty acid, and steroid metabolism, nucleoside, nucleotide and nucleic acid metabolism, immunity and defense, and carbohydrate metabolism. Gene interaction network analysis showed a common network that was common to the different tissues of the Cmah null mouse. However, the expression of most sialytransferase mRNAs of Hanganutziu-Deicher antigen, sialy-Tn antigen, Forssman antigen, and Tn antigen was significantly down-regulated in the liver tissue of Cmah null mice.

Conclusions/significance: Mice bearing a human-like deletion of the Cmah gene serve as an important model for the study of abnormal pathogenesis and/or metabolism caused by the evolutionary loss of Neu5Gc synthesis in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Knockout Techniques
  • Gene Ontology
  • Gene Regulatory Networks
  • Genotype
  • Immunohistochemistry
  • Kidney / metabolism*
  • Lung / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism*
  • Myocardium / metabolism*
  • Protein Interaction Maps
  • Sialyltransferases / genetics
  • Sialyltransferases / metabolism
  • Signal Transduction*
  • Transcriptome


  • Mixed Function Oxygenases
  • CMPacetylneuraminate monooxygenase
  • Sialyltransferases

Associated data

  • GEO/GSE59964

Grant support

This work was supported by the next generation of Biogreen 21 (PJ009625) from the Rural Development Administration (RDA), Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.