These targeted mutation mice carry a functional knockout of the Oscar gene, disrupting a pathways associated with osteoclastogenesis. These mice may be useful in studies of bone remodeling and the pathological bone loss observed in autoimmune diseases, such as osteoporosis and rheumatoid arthritis, and bone cancers.
Marco Colonna, Washington University School of Medicine
Oscar (osteoclast associated receptor) is a collagen receptor, specifically expressed by pre-osteoclasts, that acts as a costimulatory signal for the Fc receptor common gamma (FcRg)-associated pathway required for osteoclastogenesis.
To better define the role of Oscar in osteoclast differentiation, knockout mice were generated. Animals homozygous for a Oscar knockout do not exhibit any difference in bone volume when compared with wildtype mice.
When the Oscar knockout is combined with a Tyrobp (Dap12) knockout, animals show decreased osteoclast numbers, decreased osteoclast size, and a reduction in eroded bone surfaces as compared to animals homozygous for a Tyrobp targeted mutation. The number and volume of trabeculae in bones is increased. Osteoblast numbers and bone formation parameters are unchanged.
These mice may be useful in studies of bone remodeling and the pathological bone loss observed in autoimmune diseases, such as osteoporosis and rheumatoid arthritis, and bone cancers.
An approximately 3 kb region encoding the entire extracellular domain (exons 3 and 4) and transmembrane domain (exon 5) was deleted from the gene and replaced with a neomycin drug resistance cassette. The mutation was created in E14.1 129P2/OlaHsd-derived embryonic stem (ES) cells. Animals were backcrossed to C57BL/6J to create speed congenics with a greater than 99% C57BL/6 background.
|Allele Name||targeted mutation 1, Yongwon Choi|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Oscar, osteoclast associated receptor|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A 3.0 kb segment, containing the entire extracellular domain (exon 3 and 4) and transmembrane domain (exon 5), was deleted.|
Animals homozygous for both mutations are viable and fertile.
When using the B6.129P2-Oscartm1Ywc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018053 in your Materials and Methods section.