Linked Life Data

10407039

Source:http://linkedlifedata.com/resource/pubmed/id/10407039

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1999-8-2
pubmed:abstractText
Cyclin-dependent kinase 5 (Cdk5) is a member of the family of cell cycle-related kinases. Previous neuropathological analysis of cdk5(-/-) mice showed significant changes in CNS development in regions from cerebral cortex to brainstem. Among the defects in these animals, a disruption of the normal pattern of cell migrations in cerebellum was particularly apparent, including a pronounced abnormality in the location of cerebellar Purkinje cells. Complete analysis of this brain region is hampered in the mutant because most of cerebellar morphogenesis occurs after birth and the cdk5(-/-) mice die in the perinatal period. To overcome this disadvantage, we have generated chimeric mice by injection of cdk5(-/-) embryonic stem cells into host blastocysts. Analysis of the cerebellum from the resulting cdk5(-/-) left arrow over right arrow cdk5(+/+) chimeric mice shows that the abnormal location of the mutant Purkinje cells is a cell-autonomous defect. In addition, significant numbers of granule cells remain located in the molecular layer, suggesting a failure to complete migration from the external to the internal granule cell layer. In contrast to the Purkinje and granule cell populations, all three of the deep cerebellar nuclear cell groupings form correctly and are composed of cells of both mutant and wild-type genotypes. Despite similarities of the cdk5(-/-) phenotype to that reported in reeler and mdab-1(-/-) (scrambler/yotari) mutant brains, reelin and disabled-1 mRNA were found to be normal in cdk5(-/-) brain. Together, the data further support the hypothesis that Cdk5 activity is required for specific components of neuronal migration that are differentially required by different neuronal cell types and by even a single neuronal cell type at different developmental stages.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6017-26
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10407039-Aging, pubmed-meshheading:10407039-Animals, pubmed-meshheading:10407039-Blastocyst, pubmed-meshheading:10407039-Cell Adhesion Molecules, Neuronal, pubmed-meshheading:10407039-Cerebellum, pubmed-meshheading:10407039-Chimera, pubmed-meshheading:10407039-Cyclin-Dependent Kinase 5, pubmed-meshheading:10407039-Cyclin-Dependent Kinases, pubmed-meshheading:10407039-Extracellular Matrix Proteins, pubmed-meshheading:10407039-Mice, pubmed-meshheading:10407039-Mice, Inbred C57BL, pubmed-meshheading:10407039-Mice, Inbred Strains, pubmed-meshheading:10407039-Mice, Knockout, pubmed-meshheading:10407039-Morphogenesis, pubmed-meshheading:10407039-Nerve Tissue Proteins, pubmed-meshheading:10407039-Purkinje Cells, pubmed-meshheading:10407039-RNA, Messenger, pubmed-meshheading:10407039-Serine Endopeptidases, pubmed-meshheading:10407039-Stem Cells, pubmed-meshheading:10407039-Transcription, Genetic
pubmed:year
1999
pubmed:articleTitle
Migration defects of cdk5(-/-) neurons in the developing cerebellum is cell autonomous.
pubmed:affiliation
Functional Genomics Unit, Gene Targeting Facility, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't