Caetano-Lopes, J.Lessard, S. G.Hann, S.Espinoza, K.Kang, Kyung ShinLim, Kyung-EunHoran, Dan J.Noonan, H. R.Hu, D.Baron, R.Robling, Alexander G.Warman, M. L.2017-11-152017-11-152017-12Caetano-Lopes, J., Lessard, S. G., Hann, S., Espinoza, K., Kang, K. S., Lim, K. E., … Warman, M. L. (2017). Clcn7F318L/+ as a new mouse model of Albers-Schönberg disease. Bone, 105, 253-261. https://doi.org/10.1016/j.bone.2017.09.007https://hdl.handle.net/1805/14551Dominant 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.enPublisher PolicyosteopetrosisAlbers-Schönberg diseaseosteoclastArticle