Linked Life Data

18434326

Source:http://linkedlifedata.com/resource/pubmed/id/18434326

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2008-7-16
pubmed:databankReference
pubmed:abstractText
Deficient enzymatic activity of the mitochondrial deoxyribonucleoside kinases deoxyguanosine kinase (DGUOK) or thymidine kinase 2 (TK2) cause mitochondrial DNA (mtDNA)-depletion syndromes in humans. Here we report the generation of a Tk2-deficient mouse strain and show that the mice develop essentially normally for the first week but from then on exhibit growth retardation and die within 2-4 weeks of life. Several organs including skeletal muscle, heart, liver and spleen showed progressive loss of mtDNA without increased mtDNA mutations or structural alterations. There were no major histological changes in skeletal muscle, but heart muscle showed disorganized and damaged muscle fibers. Electron microscopy showed mitochondria with distorted cristae. The Tk2-deficient mice exhibited pronounced hypothermia and showed loss of hypodermal fat and abnormal brown adipose tissue. We conclude that Tk2 has a major role in supplying deoxyribonucleotides for mtDNA replication and that other pathways of deoxyribonucleotide synthesis cannot compensate for loss of this enzyme.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2329-35
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Progressive loss of mitochondrial DNA in thymidine kinase 2-deficient mice.
pubmed:affiliation
Department of Laboratory Medicine, Karolinska Institute, S-141 86 Huddinge, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't