Osteopetrosis in Src-deficient mice is due to an autonomous defect of osteoclasts

Carolyn Lowe, Toshiyuki Yoneda, Brendan F. Boyce, Hong Chen, Gregory R. Mundy, Philippe Soriano

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286 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)4485-4489
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - May 15 1993


  • Gene targeting
  • Tyrosine kinases

ASJC Scopus subject areas

  • General


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