Linked Life Data

12514218

Source:http://linkedlifedata.com/resource/pubmed/id/12514218

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-1-6
pubmed:abstractText
Hormones and nuclear receptors (NRs) play important roles in brain development and function. The recently identified steroid receptor coactivator (SRC) family contains three homologous members that can enhance transcriptional activities of NRs and certain non-NR transcription factors. To study the role of SRC-1 in brain development and function, we examined the spatial and temporal expression patterns of SRC-1 and characterized the phenotypes of brain development and function in SRC-1 knock-out (SRC-1(-)/-) mice. In the adult mouse brain, SRC-1 is highly expressed in the olfactory bulb, hippocampus, piriform cortex, amygdala, hypothalamus, cerebellum, and brainstem. Multiple behavioral tests revealed that SRC-1(-)/- mice exhibit normal hippocampal function but moderate motor dysfunction. The behavior phenotypes correlate with the spatial distribution of the SRC family members. In most brain structures where SRC-1 is expressed, SRC-2 is expressed at lower levels; however, SRC-3 mRNA is detectable only in the hippocampus. In the adult cerebellum, Purkinje cells (PCs) preferentially express SRC-1 over SRC-2, but SRC-2 mRNA is slightly elevated in the SRC-1(-)/- PCs. During embryonic development, SRC-1 is expressed in the cerebellar primordium. SRC-2 is expressed in PCs after postnatal day (P) 10. Time course analysis revealed that the precursors of SRC-1(-)/- PCs were generated approximately 2 d later than wild-type precursor cells. A further delay in SRC-1(-)/- PC maturation was detected at the neonatal stage. The morphology and number of SRC-1(-)/- PCs were equivalent to wild type by P10; this timing correlated with the early expression of SRC-2 in the SRC-1(-)/- PCs. These results demonstrate that the relative levels of SRC expression are region specific, and the degree of overlapping expression may influence their functional redundancy. Disruption of SRC-1 specifically delays the PC development and maturation in early stages and results in moderate motor dysfunction in adulthood.
pubmed:grant
pubmed:keyword
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
213-22
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12514218-Animals, pubmed-meshheading:12514218-Behavior, Animal, pubmed-meshheading:12514218-Brain, pubmed-meshheading:12514218-Cell Culture Techniques, pubmed-meshheading:12514218-Cell Differentiation, pubmed-meshheading:12514218-Cerebellar Cortex, pubmed-meshheading:12514218-Histone Acetyltransferases, pubmed-meshheading:12514218-Mice, pubmed-meshheading:12514218-Mice, Inbred C57BL, pubmed-meshheading:12514218-Mice, Knockout, pubmed-meshheading:12514218-Motor Activity, pubmed-meshheading:12514218-Nuclear Receptor Coactivator 1, pubmed-meshheading:12514218-Nuclear Receptor Coactivator 2, pubmed-meshheading:12514218-Nuclear Receptor Coactivator 3, pubmed-meshheading:12514218-Purkinje Cells, pubmed-meshheading:12514218-RNA, Messenger, pubmed-meshheading:12514218-Stem Cells, pubmed-meshheading:12514218-Time Factors, pubmed-meshheading:12514218-Trans-Activators, pubmed-meshheading:12514218-Transcription Factors
pubmed:year
2003
pubmed:articleTitle
SRC-1 null mice exhibit moderate motor dysfunction and delayed development of cerebellar Purkinje cells.
pubmed:affiliation
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't