Generation of the first autosomal dominant osteopetrosis type II (ADO2) disease models
Copyright policy )Generation of the first autosomal dominant osteopetrosis type II (ADO2) disease models
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.
- Istituti di Ricovero e Cura a Carattere Scientifico Italy
- Boston Children's Hospital United States
- Indiana University United States
- University of Padua Italy
- ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO BURLO GAROFOLO Italy
Male, Heterozygote, Chloride channel 7, Molecular Sequence Data, Osteoclasts, Osteopetrosis; Chloride channel; Osteoclast, Bone and Bones, Mouse model, Mice, Bone Density, Chloride Channels, Autosomal dominant osteopetrosis, Animals, Gene Knock-In Techniques, Cells, Cultured, Genes, Dominant, Neurons, Base Sequence, Homozygote, Mice, Inbred C57BL, Disease Models, Animal, Osteopetrosis, Osteoclast, Female, Biomarkers
Male, Heterozygote, Chloride channel 7, Molecular Sequence Data, Osteoclasts, Osteopetrosis; Chloride channel; Osteoclast, Bone and Bones, Mouse model, Mice, Bone Density, Chloride Channels, Autosomal dominant osteopetrosis, Animals, Gene Knock-In Techniques, Cells, Cultured, Genes, Dominant, Neurons, Base Sequence, Homozygote, Mice, Inbred C57BL, Disease Models, Animal, Osteopetrosis, Osteoclast, Female, Biomarkers
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