Linked Life Data

20046060

Source:http://linkedlifedata.com/resource/pubmed/id/20046060

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-1-4
pubmed:abstractText
Manganese superoxide dismutase (Mn-SOD) is a mitochondrial enzyme that converts toxic O(2)(-) to H(2)O(2). Previous studies have reported that a systemic deficiency in Mn-SOD causes neonatal lethality in mice. Therefore, no mouse model is available for the analysis of the pathological role of O(2)(-) injuries in adult tissues. To explore an adult-type mouse model, we generated tissue-specific Mn-SOD conditional knockout mice using a Cre-loxp system. First, we generated liver-specific Mn-SOD-deficient mice by crossbreeding with albumin-Cre transgenic mice. Mn-SOD proteins were significantly downregulated in the liver of liver-specific Mn-SOD knockout mice. Interestingly, the mutant mice showed no obvious morphological abnormalities or biochemical alterations in the liver, suggesting a redundant or less important physiological role for Mn-SOD in the liver than previously thought. Next, we generated heart/muscle-specific Mn-SOD-deficient mice by crossbreeding with muscle creatine kinase-Cre transgenic mice. The mutant mice developed progressive dilated cardiomyopathy with specific molecular defects in mitochondrial respiration. Furthermore, skeletal muscle-specific Mn-SOD-deficient mice that had been generated by crossbreeding with human skeletal actin-Cre transgenic mice developed a severe physical disturbance associated with impaired cellular ATP metabolism. These results imply that the superoxide generated in mitochondria plays a pivotal role in the development and progression of pathologies in the heart and skeletal muscle, but not in the liver. In conclusion, we successfully generated various tissue-specific Mn-SOD conditional knockout mice that provide useful tools for the analysis of various oxidative stress-associated diseases.
pubmed:language
jpn
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0031-6903
pubmed:author
pubmed:issnType
Print
pubmed:volume
130
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19-24
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
[Anti-aging research using Mn-SOD conditional knockout mice].
pubmed:affiliation
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. shimizut@tmig.or.jp
pubmed:publicationType
Journal Article, English Abstract, Review