Linked Life Data

17467682

Source:http://linkedlifedata.com/resource/pubmed/id/17467682

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-6-11
pubmed:abstractText
Small GTPases of the Rho family have been implicated in the regulation of many intracellular processes. However, their tissue-specific roles in mammalian growth and development in vivo remain largely unknown. Here we describe the effects of cartilage-specific inactivation of the Rac1 gene in mice. Mice carrying this mutation show increased lethality, skeletal deformities, severe kyphosis and dwarfism. Rac1-deficient growth plates are disorganized and hypocellular, with chondrocytes of abnormal shape and size. Rac1-deficient chondrocytes also display reduced adhesion and spreading on collagen II and fibronectin as well as altered organization of the actin cytoskeleton, suggesting that Rac1 is required for normal cell-extracellular matrix interactions in cartilage. This phenotype is accompanied by reduced proliferation, increased apoptosis and deregulated expression of the cell cycle genes cyclin D1 and p57 in vivo. Moreover, phosphorylation of p38 MAP kinases is greatly reduced and expression of a key regulator of cartilage development, Indian hedgehog, is increased in mutant mice. In summary, these data identify a novel, essential and tissue-specific role of Rac1 in skeletal development and demonstrate that Rac1 deficiency affects numerous regulatory pathways in cartilage.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0012-1606
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
306
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
612-23
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Genetic ablation of Rac1 in cartilage results in chondrodysplasia.
pubmed:affiliation
CIHR Group in Skeletal Development and Remodeling, Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't