Massive osteopetrosis caused by non-functional osteoclasts in R51Q SNX10 mutant mice

Merle Stein, Maayan Barnea-Zohar, Moran Shalev, Esther Arman, Ori Brenner, Sabina Winograd-Katz, Jennifer Gerstung, Fadi Thalji, Moien Kanaan, Hila Elinav, Polina Stepensky, Benny Geiger, Jan Tuckermann, Ari Elson

Research output: Contribution to journalArticlepeer-review

Abstract

The R51Q mutation in sorting nexin 10 (SNX10) was shown to cause a lethal genetic disease in humans, namely autosomal recessive osteopetrosis (ARO). We describe here the first R51Q SNX10 knock-in mouse model and show that mice homozygous for this mutation exhibit massive, early-onset, and widespread osteopetrosis. The mutant mice exhibit multiple additional characteristics of the corresponding human disease, including stunted growth, failure to thrive, missing or impacted teeth, occasional osteomyelitis, and a significantly-reduced lifespan. Osteopetrosis in this model is the result of osteoclast inactivity that, in turn, is caused by absence of ruffled borders in the mutant osteoclasts and by their inability to secrete protons. These results confirm that the R51Q mutation in SNX10 is a causative factor in ARO and provide a model system for studying this rare disease.
Original languageEnglish
Article number115360
Number of pages14
JournalBone
Volume136
Early online date8 Apr 2020
DOIs
StatePublished - Jul 2020

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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