Journal article

Extra-skeletal manifestations in mice affected by Clcn7-dependent autosomal dominant osteopetrosis type 2 clinical and therapeutic implications

Antonio Maurizi, Mattia Capulli, Annabel Curle, Rajvi Patel, Argia Ucci, Juliana Alves Cortes, Harriet Oxford, Shireen R Lamande, John F Bateman, Nadia Rucci, Anna Teti



Autosomal dominant osteopetrosis type 2 (ADO2) is a high-density brittle bone disease characterized by bone pain, multiple fractures and skeletal-related events, including nerve compression syndrome and hematological failure. We demonstrated that in mice carrying the heterozygous Clcn7 G213R mutation, whose human mutant homolog CLCN7 G215R affects patients, the clinical impacts of ADO2 extend beyond the skeleton, affecting several other organs. The hallmark of the extra-skeletal alterations is a consistent perivascular fibrosis, associated with high numbers of macrophages and lymphoid infiltrates. Fragmented clinical information in a small cohort of patients confirms extra-skeletal alteratio..

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Awarded by Fondazione Telethon

Awarded by European Union

Awarded by Progetti di Rilevante Interesse Nazionale (PRIN)

Funding Acknowledgements

This work was supported by the Fondazione Telethon Grants GGP09018 and GGP14014, the European Union funded project SYBIL-FP7-HEALTH-2013-INNOVATION-602300 and by the Progetti di Rilevante Interesse Nazionale (PRIN) grant 2015F3JHMB to A.T. A.M. and A.U. were recipients of Marie Curie fellowships from the European Union funded project RUBICON-H2020-MSCA-RISE-2015_690850 to A.T. We are indebted with Prof. Paul A. Gleeson, University of Melbourne Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, for his advice in the Golgi studies, and with Dr. Rita Di Massimo for editing the paper.