title: CMP-Neu5Ac Hydroxylase Null Mice as a Model for Studying Metabolic Disorders Caused by the Evolutionary Loss of Neu5Gc in Humans.
abstract: 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.
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Deug-Nam
authors.initials: DN
authors.lastname: Kwon
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Ssang-Goo
authors.initials: SG
authors.lastname: Cho
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Chankyu
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000235:genetics* / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D009438:Neuraminic Acids / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics
chemical_list: D009438:Neuraminic Acids; C032592:N-glycolylneuraminic acid; D006899:Mixed Function Oxygenases; C074383:CMPacetylneuraminate monooxygenase