Linked Life Data

10802668

Source:http://linkedlifedata.com/resource/pubmed/id/10802668

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-6-12
pubmed:abstractText
Myotonic dystrophy (DM) is an autosomal dominant disorder characterized by skeletal muscle wasting, myotonia, cardiac arrhythmia, hyperinsulinaemia, mental retardation and ocular cataracts. The genetic defect in DM is a CTG repeat expansion located in the 3' untranslated region of DMPK and 5' of a homeodomain-encoding gene, SIX5 (formerly DMAHP; refs 2-5). There are three mechanisms by which CTG expansion can result in DM. First, repeat expansion may alter the processing or transport of the mutant DMPK mRNA and consequently reduce DMPK levels. Second, CTG expansion may establish a region of heterochromatin 3' of the repeat sequence and decrease SIX5 transcription. Third, toxic effects of the repeat expansion may be intrinsic to the repeated elements at the level of DNA or RNA (refs 10,11). Previous studies have demonstrated that a dose-dependent loss of Dm15 (the mouse DMPK homologue) in mice produces a partial DM phenotype characterized by decreased development of skeletal muscle force and cardiac conduction disorders. To test the role of Six5 loss in DM, we have analysed a strain of mice in which Six5 was deleted. Our results demonstrate that the rate and severity of cataract formation is inversely related to Six5 dosage and is temporally progressive. Six5+/- and Six5-/- mice show increased steady-state levels of the Na+/K+-ATPase alpha-1 subunit and decreased Dm15 mRNA levels. Thus, altered ion homeostasis within the lens may contribute to cataract formation. As ocular cataracts are a characteristic feature of DM, these results demonstrate that decreased SIX5 transcription is important in the aetiology of DM. Our data support the hypothesis that DM is a contiguous gene syndrome associated with the partial loss of both DMPK and SIX5.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
110-4
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Heterozygous loss of Six5 in mice is sufficient to cause ocular cataracts.
pubmed:affiliation
Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't