Linked Life Data

11042023

Source:http://linkedlifedata.com/resource/pubmed/id/11042023

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-11-29
pubmed:abstractText
Insulin-like growth factors (IGFs) produced in the brain are known to participate in brain development via activation of the type 1 IGF receptor. IGF binding proteins (IGFBPs) modulate the cellular action of IGFs and some are expressed in the fetal brain. Under normal conditions IGFBP-1 is not one of these, but IGFBP-1 expression obtained via transgenesis using ubiquitous promoters affects brain development. In earlier work, we established a model of transgenic mouse in which liver-specific IGFBP-1 expression begins during fetal life. The repercussions of this IGFBP-1 over-expression include reproductive defects, ante- and perinatal mortality and post-natal growth retardation, the extent of which is related to the degree of transgene expression. Unexpectedly, during the first 2 months of postnatal life, there were some cases of head enlargement revealing hydrocephalus among homozygotes, frequently associated with motor disorders. Brain sections showed dilatation of the lateral ventricles in 10 out of 15 homozygotes examined. Histologically, dilatation was evident in four out of nine heterozygotes. Brain weight in transgenics was relatively less reduced than the weights of other organs. Hence, brain weight/body weight ratios were normal in heterozygotes and on average higher than normal in homozygotes. The width of the cerebral cortex was reduced in homozygotes, with disorganized neuronal layers. The corpus callosum was underdeveloped, particularly in homozygotes. The area of the hippocampus was reduced in homozygotes and one-third of the heterozygotes, with a short and thick dentate gyrus in the former. Similar anomalies have been reported in mice with disruption of the igf-I gene and in a model of transgenic mice over-expressing IGFBP-1 in all tissues, including the brain. Hydrocephalus was not mentioned in these reports, raising the possibility that insertional mutagenesis may have been involved in our mice. Nevertheless, our observations indicate that hepatic over-expression of IGFBP-1 may have endocrine effects on brain development.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1096-6374
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Harcourt Publishers Ltd.
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
267-74
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Impaired brain development and hydrocephalus in a line of transgenic mice with liver-specific expression of human insulin-like growth factor binding protein-1.
pubmed:affiliation
INSERM U.515, Hôpital Saint Antoine, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't