Osteopetrosis in Src-Deficient Mice is Due to an Autonomous Defect of Osteoclasts

Osteopetrosis is a bone modeling disorder resulting in excessive accumulation of bone matrix due to defective function of osteoclasts, the cells that resorb bone. Mice carrying a targeted disruption of the gene Src that encodes pp60c-src(Src), a nonreceptor protein tyrosine kinase, develop this phen...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1993-05, Vol.90 (10), p.4485-4489
Main Authors: Lowe, Carolyn, Yoneda, Toshiyuki, Boyce, Brendan F., Chen, Hong, Mundy, Gregory R., Soriano, Philippe
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Bone Resorption
Bones
Cells
Cells, Cultured
Cellular biology
Coculture techniques
Cytoplasm
Diseases of the osteoarticular system
Genes, src
Immunoenzyme Techniques
In Vitro Techniques
Liver - cytology
Liver - embryology
Liver cells
Liver Transplantation
Malformations and congenital and or hereditary diseases involving bones. Joint deformations
Medical sciences
Mice
Mice, Mutant Strains
Osteoblasts
Osteoclasts
Osteoclasts - physiology
Osteopetrosis
Osteopetrosis - pathology
Osteopetrosis - physiopathology
Protein-Tyrosine Kinases - physiology
Proto-Oncogene Proteins pp60(c-src) - deficiency
Rodents
Skeletal system
Spleen cells
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Osteopetrosis is a bone modeling disorder resulting in excessive accumulation of bone matrix due to defective function of osteoclasts, the cells that resorb bone. Mice carrying a targeted disruption of the gene Src that encodes pp60c-src(Src), a nonreceptor protein tyrosine kinase, develop this phenotype but do not exhibit other overt defects despite the fact that the kinase is normally present in a broad variety of cell types. Because Src is expressed in osteoblasts as well as in osteoclasts and both are required for normal bone resorption, the basic defect could occur in either cell type. In this study we have used in vitro approaches and fetal liver transplantation into irradiated Src-recipients to demonstrate that the inherent defect is with osteoclasts and autonomous of the bone marrow microenvironment. This result (i) identifies a cell type in which Src function is essential and cannot be replaced by other related kinases and (ii) should allow the isolation of a substrate that is specific to Src.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.90.10.4485