Generation of the first autosomal dominant osteopetrosis type II (ADO2) disease models

Imranul Alam, Amie K. Gray, Kang Chu, Shoji Ichikawa, Khalid S. Mohammad, Marta Capannolo, Mattia Capulli, Antonio Maurizi, Maurizio Muraca, Anna Teti, Michael J. Econs, Andrea Del Fattore

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)66-75
Number of pages10
Publication statusPublished - 2014


  • Autosomal dominant osteopetrosis
  • Chloride channel 7
  • Mouse model
  • Osteoclast
  • Osteopetrosis

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology


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