Linked Life Data

12623879

Source:http://linkedlifedata.com/resource/pubmed/id/12623879

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-4-4
pubmed:abstractText
Despite the advantages of reversibly altering cardiac transgene expression, the number of successful studies with inducible cardiac-specific transgene expression remains limited. The utility of the current system is hampered by the large number of lines needed before a nonleaky inducible line is isolated and by the use of a heterologous virus-based minimal promoter in the responder line. We developed an efficient, experimentally flexible system that enables us to reversibly affect both abundant and nonabundant cardiomyocyte proteins. The use of bacterial-codon-based transactivators led to aberrant splicing, whereas other more efficient transactivators, by themselves, caused disease when expressed in the heart. The redesign of the system focused on developing stable transactivator-expressing lines in which expression was driven by the mouse alpha-myosin heavy chain promoter. A minimal responder locus was derived from the same promoter, in which the GATA sites and thyroid responsive elements responsible for robust cardiac specific expression were ablated, leading to an attenuated promoter that could be inducibly controlled. In all cases, whether activated or not, expression mimicked that of the parental promoter. By use of this system, an inducible expression of an abundant contractile protein, the atrial isoform of essential myosin light chain 1, and a powerful biological effector, glycogen synthase kinase-3beta (GSK-3beta), were obtained. Subsequently, we tested the hypothesis that GSK-3beta expression could reverse a preexisting hypertrophy. Inducible expression of GSK-3beta could both attenuate a hypertrophic response and partially reverse a pressure-overload-induced hypertrophy. The system appears to be robust and can be used to temporally control high levels of cardiac-specific transgene expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
4
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
609-16
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:12623879-Animals, pubmed-meshheading:12623879-Cardiomegaly, pubmed-meshheading:12623879-DNA, Complementary, pubmed-meshheading:12623879-Genetic Engineering, pubmed-meshheading:12623879-Glycogen Synthase Kinase 3, pubmed-meshheading:12623879-Herpes Simplex Virus Protein Vmw65, pubmed-meshheading:12623879-Mice, pubmed-meshheading:12623879-Mice, Transgenic, pubmed-meshheading:12623879-Myocardium, pubmed-meshheading:12623879-Myosin Heavy Chains, pubmed-meshheading:12623879-Myosin Light Chains, pubmed-meshheading:12623879-Promoter Regions, Genetic, pubmed-meshheading:12623879-RNA Splicing, pubmed-meshheading:12623879-Sarcomeres, pubmed-meshheading:12623879-Sequence Deletion, pubmed-meshheading:12623879-Tetracycline, pubmed-meshheading:12623879-Transcriptional Activation, pubmed-meshheading:12623879-Transgenes
pubmed:year
2003
pubmed:articleTitle
Reengineering inducible cardiac-specific transgenesis with an attenuated myosin heavy chain promoter.
pubmed:affiliation
Department of Pediatrics, Division of Molecular Cardiovascular Biology, MLC7020 The Children's Hospital Research Foundation, Cincinnati, OH 45229-3039, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't