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

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 norm...

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Bibliographic Details
Published in:BioMed research international 2015-01, Vol.2015 (2015), p.1-16
Main Authors: Kim, Jin-Hoi, Seo, Han Geuk, Park, Chankyu, Cho, Ssang-Goo, Choi, Yun-Jung, Kwon, Deug-Nam, Song, Hyuk
Format: Article
Language:English
Subjects:
Animals
Cluster Analysis
Diabetes
Disease Models, Animal
Evolution, Molecular
Gene expression
Gene Regulatory Networks - genetics
Genomes
Genotype & phenotype
Health aspects
Humans
Hydroxylases
Lipids
Male
Metabolic diseases
Metabolic disorders
Mice
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs
Mitochondria, Liver - genetics
Mitochondria, Liver - metabolism
Mixed Function Oxygenases - deficiency
Mixed Function Oxygenases - genetics
Mixed Function Oxygenases - metabolism
Mutation
Neuraminic Acids - metabolism
Oxidative Stress - genetics
Pathogens
Physiological aspects
Typhoid
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Summary: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.
ISSN:2314-6133
2314-6141
DOI:10.1155/2015/830315