Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification
| Autor: | Yi-Ping Li, En Li, Philip Stashenko, Wei Chen, Yuqiong Liang |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Vacuolar Proton-Translocating ATPases Protein subunit Osteoclasts Biology Kidney Mice Osteoclast Proton transport Genetics medicine Extracellular Animals Tissue Distribution RNA Messenger Bone Resorption Mice Knockout Hydrogen-Ion Concentration Proton Pumps Cell biology Mice Inbred C57BL Proton-Translocating ATPases medicine.anatomical_structure Phenotype Biochemistry Liver Osteopetrosis biology.protein Female CLCN7 Extracellular Space Intracellular Infantile malignant osteopetrosis |
| Zdroj: | Nature genetics. 23(4) |
| ISSN: | 1061-4036 |
| Popis: | Solubilization of bone mineral by osteoclasts depends on the formation of an acidic extracellular compartment through the action of a V-proton pump that has not yet been characterized at the molecular level. We previously cloned a gene (Atp6i, for V-proton pump, H+ transporting (vacuolar proton pump) member I) encoding a putative osteoclast-specific proton pump subunit, termed OC-116kD (ref. 4). Here we show that targeted disruption of Atp6i in mice results in severe osteopetrosis. Atp6i-/- osteoclast-like cells (OCLs) lose the function of extracellular acidification, but retain intracellular lysosomal proton pump activity. The pH in Atp6i-/- liver lysosomes and proton transport in microsomes of Atp6i-/- kidney are identical to that in wild-type mice. Atp6i-/- mice exhibit a normal acid-base balance in blood and urine. Our results demonstrate that Atp6i is unique and necessary for osteoclast-mediated extracellular acidification. |
| Databáze: | OpenAIRE |
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