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Updated: Jul 26, 2026
A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
Published on: June 8, 2014
A novel putative transporter maps to the osteosclerosis (oc) mutation and is not expressed in the oc mutant mouse
K P Brady1, H Dushkin, D Förnzler
1Genetics Division, Renal Division, Brigham & Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts, 02115, USA.
Abstract:
The phenotype of mice homozygous for the osteosclerosis (oc) mutation includes osteopetrosis, and a variety of studies demonstrate that osteoclasts in these mice are present but nonfunctional. We have identified a novel gene that has homology to a family of 12-transmembrane domain proteins with transport functions and maps to proximal mouse chromosome 19, in a region to which the oc mutation has been previously assigned. The putative transporter is abundant in normal kidney, but its expression is markedly reduced in kidneys from oc/oc mice when tested using Northern and Western analyses. Southern analysis of this gene, which we call Roct (reduced in oc transporter), demonstrates that it is intact and unrearranged in oc/oc mice. In situ studies show that Roct is expressed in developing bone. We propose that the absence of Roct expression results in an osteopetrosis phenotype in mice.
Insights
Researchers identified a novel gene, Roct (reduced in oc transporter), linked to osteopetrosis in mice. Reduced expression of this gene in osteosclerosis (oc) mutant mice leads to nonfunctional osteoclasts and bone disease.
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- Osteopetrosis is a bone disorder characterized by impaired osteoclast function.
- The osteosclerosis (oc) mutation in mice results in osteopetrosis with nonfunctional osteoclasts.
- The genetic basis for the oc mutation has been localized to mouse chromosome 19.
Purpose of the Study:
- To identify the gene responsible for the osteopetrosis phenotype in oc/oc mice.
- To characterize the function and expression pattern of the novel gene identified.
Main Methods:
- Positional cloning to map the gene to mouse chromosome 19.
- Northern and Western blot analyses to assess gene expression levels.
- Southern blot analysis to evaluate gene integrity.
- In situ hybridization to determine expression in developing bone.
Main Results:
- A novel gene, Roct (reduced in oc transporter), was identified with homology to transmembrane transporters.
- Roct expression is significantly reduced in the kidneys of oc/oc mice.
- Roct gene is intact and not rearranged in oc/oc mice.
- Roct is expressed in developing bone tissues.
Conclusions:
- The Roct gene is a strong candidate for the gene underlying the osteopetrosis phenotype in oc/oc mice.
- Reduced expression or function of Roct likely leads to impaired osteoclast activity and osteopetrosis.
- Roct may play a crucial role in osteoclast development or function.
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