关键词： Autosomal dominant osteopetrosis Chloride channel 7 Mouse model Osteoclast Osteopetrosis

Mesh ： Animals Base Sequence Biomarkers / blood Bone Density / genetics Bone and Bones / diagnostic imaging metabolism pathology Cells, Cultured Chloride Channels / genetics Disease Models, Animal Female Gene Knock-In Techniques Genes, Dominant Heterozygote Homozygote Male Mice Mice, Inbred C57BL Molecular Sequence Data Neurons / metabolism Osteoclasts / metabolism pathology Osteopetrosis / genetics Phenotype X-Ray Microtomography

来  源：   DOI：10.1016/j.bone.2013.10.021   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
Autosomal dominant osteopetrosis type II (ADO2) is a heritable osteosclerotic disorder dependent on osteoclast impairment. In most patients it results from heterozygous missense mutations in the chloride channel 7 (CLCN7) gene, encoding for a 2Cl(-)/1H(+) antiporter. By a knock-in strategy inserting a missense mutation in the Clcn7 gene, our two research groups independently generated mouse models of ADO2 on different genetic backgrounds carrying the homolog of the most frequent heterozygous mutation (p.G213R) in the Clcn7 gene found in humans. Our results demonstrate that the heterozygous model holds true presenting with higher bone mass, increased numbers of poorly resorbing osteoclasts and a lethal phenotype in the homozygous state. Considerable variability is observed in the heterozygous mice according with the mouse background, suggesting that modifier genes could influence the penetrance of the disease gene.
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