Clcn7F318L/+ as a new mouse model of Albers-Schönberg disease

J. Caetano-Lopes, S. G. Lessard, S. Hann, K. Espinoza, K. S. Kang, K. E. Lim, D. J. Horan, H. R. Noonan, D. Hu, R. Baron, A. G. Robling, M. L. Warman

Research output: Contribution to journalArticle

2 Scopus citations


Dominant negative mutations in CLCN7, which encodes a homodimeric chloride channel needed for matrix acidification by osteoclasts, cause Albers-Schönberg disease (also known as autosomal dominant osteopetrosis type 2). More than 25 different CLCN7 mutations have been identified in patients affected with Albers-Schönberg disease, but only one mutation (Clcn7G213R) has been introduced in mice to create an animal model of this disease. Here we describe a mouse with a different osteopetrosis-causing mutation (Clcn7F318L). Compared to Clcn7+/+ mice, 12-week-old Clcn7F318L/+ mice have significantly increased trabecular bone volume, consistent with Clcn7F318L acting as a dominant negative mutation. Clcn7F318L/F318L and Clcn7F318L/G213R mice die by 1 month of age and resemble Clcn7 knockout mice, which indicate that p.F318L mutant protein is non-functional and p.F318L and p.G213R mutant proteins do not complement one another. Since it has been reported that treatment with interferon gamma (IFN-G) improves bone properties in Clcn7G213R/+ mice, we treated Clcn7F318L/+ mice with IFN-G and observed a decrease in osteoclast number and mineral apposition rate, but no overall improvement in bone properties. Our results suggest that the benefits of IFN-G therapy in patients with Albers-Schönberg disease may be mutation-specific.

Original languageEnglish (US)
Pages (from-to)253-261
Number of pages9
StatePublished - Dec 2017


  • Albers-Schönberg disease
  • Osteopetrosis
  • interferon-gamma
  • osteoclast

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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    Caetano-Lopes, J., Lessard, S. G., Hann, S., Espinoza, K., Kang, K. S., Lim, K. E., Horan, D. J., Noonan, H. R., Hu, D., Baron, R., Robling, A. G., & Warman, M. L. (2017). Clcn7F318L/+ as a new mouse model of Albers-Schönberg disease. Bone, 105, 253-261.