Massive osteopetrosis caused by non-functional osteoclasts in R51Q SNX10 mutant mice
Autor: | Maayan Barnea-Zohar, Sabina Winograd-Katz, Polina Stepensky, Jennifer Gerstung, Fadi Thalji, Merle Stein, Hila Elinav, Jan Tuckermann, Moien Kanaan, Benjamin Geiger, Esther Arman, Ari Elson, Ori Brenner, Moran Shalev |
---|---|
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Histology Physiology Endocrinology Diabetes and Metabolism Mutant Osteoclasts 030209 endocrinology & metabolism Biology medicine.disease_cause Mice 03 medical and health sciences 0302 clinical medicine Osteoclast medicine Animals Secretion Sorting Nexins Mutation Osteopetrosis medicine.disease Molecular biology Sorting nexin 030104 developmental biology medicine.anatomical_structure Failure to thrive medicine.symptom Rare disease |
Zdroj: | Bone. 136:115360 |
ISSN: | 8756-3282 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |