Linked Life Data

12152782

Source:http://linkedlifedata.com/resource/pubmed/id/12152782

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-8-2
pubmed:abstractText
Targeted gene disruptions have revealed significant roles for caspase family members in the regulation of neuronal programmed cell death. Both caspase-3- and caspase-9-deficient mice exhibit a variably severe neurodevelopmental phenotype that may include marked ventricular zone expansion, exencephaly, and ectopic neuronal structures. Our previous studies of caspase-3- and caspase-9-deficient mice were performed using mice on mixed genetic backgrounds, raising the possibility that strain-specific generic factors influence the effects of caspase deficiency on nervous system development. To directly test this hypothesis. we backcrossed the caspase-3 mutation for 7-10 generations onto pure C57BL/6J and 129X1/SvJ genetic backgrounds. Caspase-3-deficient 129X1/SvJ mice were uniformly and severely affected. These mice died during the perinatal period and exhibited marked neural precursor cell expansion and exencephaly. In contrast, caspase-3-deficient C57BL/6J mice reached adulthood, were fertile and showed minimal brain pathology. Intercrosses of C57BL/6J and 129X1/SvJ mutants revealed that the vast majority of caspase-3-/- F1 mice displayed the severe 129X1/SvJ-"like" phenotype. These findings are consistent with an incompletely penetrant strain-dependent genetic modifier (or modifiers) that alters the neurodevelopmental consequences of caspase-3 deficiency. Since caspase-9- and Apaf-1-deficient mice also display variably severe developmental neuropathology, this strain-dependent modifier(s) may be involved in the activation of a caspase-independent death pathway; alternatively, strain-dependent compensatory caspase activation and/or its inhibition may influence the severity of the caspase-3-deficient neuronal phenotype.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-3069
pubmed:author
pubmed:issnType
Print
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
673-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Strain-dependent neurodevelopmental abnormalities in caspase-3-deficient mice.
pubmed:affiliation
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.