Linked Life Data

12074552

Source:http://linkedlifedata.com/resource/pubmed/id/12074552

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-6-20
pubmed:abstractText
Retinoids (vitamin A and its derivatives) play essential roles during vertebrate development. Vitamin A deprivation leads to severe congenital malformations affecting many tissues, including diverse neural crest cell populations and the heart. The vitamin A signal is transduced by the retinoic acid receptors (RARalpha, RARbeta, and RARgamma). However, these receptors exhibit considerable functional redundancy, as judged by the mild phenotype of RAR single null mutants relative to the defects evoked by loss of multiple RARs. To circumvent this redundancy, the endogenous RARgamma2 allele was replaced with a ligand-binding RARgamma mutant (RARgammaE(305)) by gene targeting in mouse embryonic stem (ES) cells. Chimeric embryos derived from hemizygous RARgammaE(305) ES cells displayed several defects similar to those observed in certain RAR double null mutants, including hypoplasia or absence of the caudal pharyngeal arches and myocardial deficiencies. The latter defects were not due to abnormal cardiac specification as affected hearts still expressed chamber-specific markers in an appropriate manner. Chimeras also displayed cardiac looping anomalies, which were associated with a reduction of Pitx2. This work suggests a role for RAR signaling in late looping morphogenesis and illustrates the utility of using a dominant-negative gene substitution approach to circumvent the functional redundancy inherent to the RAR family.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0012-1606
pubmed:author
pubmed:copyrightInfo
(c) 2002 Elsevier Science (USA).
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
247
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
62-75
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Chimeric analysis of retinoic acid receptor function during cardiac looping.
pubmed:affiliation
Laboratory of Molecular and Cellular Biology, Institut de Recherches Cliniques de Montréal, Québec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't