Osteopetrorickets due to Snx10 Deficiency in Mice Results from Both Failed Osteoclast Activity and Loss of Gastric Acid-Dependent Calcium Absorption

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We found that Snx10, a molecule expressed in osteoclasts, was also expressed in the stomach. Studies in tissue specific or global knock-down mice showed that Snx10 deficiency resulted in a phenotype that was a consequence of deficiencies in both osteoclasts and gastric zymogenic cells. Our studies add to a growing list of genes, including atp6i (Tcirg1), whose expression is required both in bone and stomach to maintain normal gastric acidification and calcium absorption. This work provides additional insight into the mechanisms governing the regulation of bone accrual by the gastrointestinal tract. Because osteopetrorickets has not been described clinically in Snx10-related osteopetrosis, these findings highlight the importance of considering impaired acidification in both stomach and bone in osteopetrotic patients with mutations in SNX10 and other genes with similar patterns of expression and activities. Because defects in gastric differentiation and/or gastric acidification may cause or contribute to hypocalcemia, bone insufficiency, and early death, our results suggest that dietary calcium supplementation could be a life-saving intervention in these patients.

Vyšlo v časopise: Osteopetrorickets due to Snx10 Deficiency in Mice Results from Both Failed Osteoclast Activity and Loss of Gastric Acid-Dependent Calcium Absorption. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005057
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005057

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