Linked Life Data

17591776

Source:http://linkedlifedata.com/resource/pubmed/id/17591776

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
2007-8-20
pubmed:abstractText
Citrin is the liver-type mitochondrial aspartate-glutamate carrier that participates in urea, protein, and nucleotide biosynthetic pathways by supplying aspartate from mitochondria to the cytosol. Citrin also plays a role in transporting cytosolic NADH reducing equivalents into mitochondria as a component of the malate-aspartate shuttle. In humans, loss-of-function mutations in the SLC25A13 gene encoding citrin cause both adult-onset type II citrullinemia and neonatal intrahepatic cholestasis, collectively referred to as human citrin deficiency. Citrin knock-out mice fail to display features of human citrin deficiency. Based on the hypothesis that an enhanced glycerol phosphate shuttle activity may be compensating for the loss of citrin function in the mouse, we have generated mice with a combined disruption of the genes for citrin and mitochondrial glycerol 3-phosphate dehydrogenase. The resulting double knock-out mice demonstrated citrullinemia, hyperammonemia that was further elevated by oral sucrose administration, hypoglycemia, and a fatty liver, all features of human citrin deficiency. An increased hepatic lactate/pyruvate ratio in the double knock-out mice compared with controls was also further elevated by the oral sucrose administration, suggesting that an altered cytosolic NADH/NAD(+) ratio is closely associated with the hyperammonemia observed. Microarray analyses identified over 100 genes that were differentially expressed in the double knock-out mice compared with wild-type controls, revealing genes potentially involved in compensatory or downstream effects of the combined mutations. Together, our data indicate that the more severe phenotype present in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice represents a more accurate model of human citrin deficiency than citrin knock-out mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25041-52
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17591776-Animals, pubmed-meshheading:17591776-Calcium-Binding Proteins, pubmed-meshheading:17591776-Glycerol, pubmed-meshheading:17591776-Glycerolphosphate Dehydrogenase, pubmed-meshheading:17591776-Homozygote, pubmed-meshheading:17591776-Humans, pubmed-meshheading:17591776-Membrane Transport Proteins, pubmed-meshheading:17591776-Mice, pubmed-meshheading:17591776-Mice, Inbred C57BL, pubmed-meshheading:17591776-Mice, Knockout, pubmed-meshheading:17591776-Mice, Transgenic, pubmed-meshheading:17591776-Mitochondria, pubmed-meshheading:17591776-Mitochondrial Membrane Transport Proteins, pubmed-meshheading:17591776-Mitochondrial Proteins, pubmed-meshheading:17591776-Mutation, pubmed-meshheading:17591776-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17591776-Organic Anion Transporters, pubmed-meshheading:17591776-Phosphates
pubmed:year
2007
pubmed:articleTitle
Citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice recapitulate features of human citrin deficiency.
pubmed:affiliation
Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan. takesah@tokushima.bunri-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't