Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice

P Soriano, C Montgomery, R Geske, A Bradley - Cell, 1991 - cell.com
P Soriano, C Montgomery, R Geske, A Bradley
Cell, 1991cell.com
To understand the normal, physiological role of the C-SIC proto-oncogene, a null mutation
was introduced into the gene by homologous recombination in mouse embryonic stem cells.
Two independent targeted clones were used to generate chimeras that transmitted the
mutated allele to their offspring. Intercrossing of heterorygotes gave rise to live born
homozygotes, but most of these mice died within the first few weeks of birth. Histological and
hematological examination of the homozygous mutants did not reveal detectable …
Summary
To understand the normal, physiological role of the C-SIC proto-oncogene, a null mutation was introduced into the gene by homologous recombination in mouse embryonic stem cells. Two independent targeted clones were used to generate chimeras that transmitted the mutated allele to their offspring. Intercrossing of heterorygotes gave rise to live born homozygotes, but most of these mice died within the first few weeks of birth. Histological and hematological examination of the homozygous mutants did not reveal detectable abnormalities in the brain or platelets, where src is most highly expressed. However, these mutants were deficient in bone remodeling, indicating impaired osteoclast function, and developed osteopetrosis. These results demonstrate that SIC is not required for general cell viability (possibly because of functional overlap with other tyrosine kinases related to SIC) and uncover an essential role for WC in bone formation.
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