Linked Life Data

11742006

Source:http://linkedlifedata.com/resource/pubmed/id/11742006

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-2-18
pubmed:abstractText
The microsomal flavoprotein NADPH-cytochrome P450 oxidoreductase (CYPOR) is believed to function as the primary, if not sole, electron donor for the microsomal cytochrome P450 mixed-function oxidase system. Development of the mammalian embryo is dependent upon temporally and spatially regulated expression of signaling factors, many of which are synthesized and/or degraded via the cytochromes P450 and other pathways involving NADPH-cytochrome P450 oxidoreductase as the electron donor. Expression of CYPOR as early as the two-cell stage of embryonic development (The Institute for Genomic Research Mouse Gene Index, version 5.0, www.tigr.org/tdb/mgi) suggests that CYPOR is essential for normal cellular functions and/or early embryogenesis. Targeted deletion of the translation start site and membrane-binding domain of CYPOR abolished microsomal CYPOR expression and led to production of a truncated, 66-kDa protein localized to the cytoplasm. Although early embryogenesis was not affected, a variety of embryonic defects was observable by day 10.5 of gestation, leading to lethality by day 13.5. Furthermore, a deficiency of heterozygotes was observed in 2-week-old mice as well as late gestational age embryos, suggesting that loss of one CYPOR allele produced some embryonic lethality. CYPOR -/- embryos displayed a marked friability, consistent with defects in cell adhesion. Ninety percent of CYPOR -/- embryos isolated at days 10.5 or 11.5 of gestation could be classified as either Type I, characterized by grossly normal somite formation but having neural tube, cardiac, eye, and limb abnormalities, or Type II, characterized by a generalized retardation of development after approximately day 8.5 of gestation. No CYPOR -/- embryos were observed after day 13.5 of gestation. These studies demonstrate that loss of microsomal CYPOR does not block early embryonic development but is essential for progression past mid-gestation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6536-41
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Association of multiple developmental defects and embryonic lethality with loss of microsomal NADPH-cytochrome P450 oxidoreductase.
pubmed:affiliation
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706-1599, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.