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

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)66-75
Number of pages10
JournalBone
Volume59
DOIs
StatePublished - 2014

Fingerprint

Osteopetrosis
Osteoclasts
Missense Mutation
Genes
Modifier Genes
Antiporters
Chloride Channels
Penetrance
Phenotype
Bone and Bones
Mutation
Research

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Generation of the first autosomal dominant osteopetrosis type II (ADO2) disease models. / Alam, Imranul; Gray, Amie K.; Chu, Kang; Ichikawa, Shoji; Mohammad, Khalid; Capannolo, Marta; Capulli, Mattia; Maurizi, Antonio; Muraca, Maurizio; Teti, Anna; Econs, Michael; Del Fattore, Andrea.

In: Bone, Vol. 59, 2014, p. 66-75.

Research output: Contribution to journalArticle

Alam, I, Gray, AK, Chu, K, Ichikawa, S, Mohammad, K, Capannolo, M, Capulli, M, Maurizi, A, Muraca, M, Teti, A, Econs, M & Del Fattore, A 2014, 'Generation of the first autosomal dominant osteopetrosis type II (ADO2) disease models', Bone, vol. 59, pp. 66-75. https://doi.org/10.1016/j.bone.2013.10.021
Alam, Imranul ; Gray, Amie K. ; Chu, Kang ; Ichikawa, Shoji ; Mohammad, Khalid ; Capannolo, Marta ; Capulli, Mattia ; Maurizi, Antonio ; Muraca, Maurizio ; Teti, Anna ; Econs, Michael ; Del Fattore, Andrea. / Generation of the first autosomal dominant osteopetrosis type II (ADO2) disease models. In: Bone. 2014 ; Vol. 59. pp. 66-75.
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