Linked Life Data

11709534

Source:http://linkedlifedata.com/resource/pubmed/id/11709534

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2001-11-15
pubmed:abstractText
We have previously constructed lines of heteroplasmic mice from two inbred strains (NZB/BinJ and BALB/c) to investigate the mechanisms of segregation of mtDNA sequence variants. Analysis of the segregation behaviour of mtDNA in several tissues showed that the NZB genotype was invariably selected in liver/kidney and the BALB genotype in blood/spleen. Segregation was not significant in post-mitotic tissues. Here we have investigated this novel pattern of mtDNA segregation in isolated hepatocytes to determine the mechanism of selection. Polarographic measurements of respiratory chain function showed no difference between mitochondria containing either 0 or 91-97% NZB mtDNAs on a BALB nuclear background. Single-cell PCR analysis of mtDNA in isolated hepatocytes demonstrated that most hepatocytes eventually fix the NZB genotype. The rate of selection was constant with time and independent of the initial genotype frequency. Based on a mtDNA replication rate of 9.4 days, NZB mtDNA has an approximately 14% selective advantage over BALB mtDNA; however, in vivo pulse labelling with BrdU demonstrated that this was not based on efficiency of replication. Surprisingly, when hepatocytes were cultured in vitro, the majority of independent colonies selected BALB mtDNA, even if they were nearly fixed for the NZB mtDNA genotype when initially plated. These data suggest that selection for NZB mtDNA in the liver of these mice is not based on respiratory chain function at the cellular or organellar level, or a simple replicative advantage, but on a factor(s) involved with mtDNA maintenance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2469-79
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Selection of a mtDNA sequence variant in hepatocytes of heteroplasmic mice is not due to differences in respiratory chain function or efficiency of replication.
pubmed:affiliation
Montreal Neurological Institute and Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't