由于破骨细胞介导的细胞外酸化丧失，Atp6i基因缺陷小鼠表现出严重的骨质硬化。

Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification.

作者信息

Li Y P, Chen W, Liang Y, Li E, Stashenko P

机构信息

Department of Cytokine Biology, The Forsyth Institute, Boston, Massachusetts, USA.

出版信息

Nat Genet. 1999 Dec;23(4):447-51. doi: 10.1038/70563.

DOI:10.1038/70563

PMID:10581033

Abstract

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.

摘要

破骨细胞对骨矿物质的溶解作用依赖于通过一种尚未在分子水平上得到表征的V质子泵的作用形成酸性细胞外区室。我们之前克隆了一个基因（Atp6i，即V质子泵，H⁺转运（液泡质子泵）成员I），该基因编码一种假定的破骨细胞特异性质子泵亚基，称为OC - 116kD（参考文献4）。在此我们表明，小鼠中Atp6i的靶向破坏会导致严重的骨硬化症。Atp6i⁻/⁻破骨细胞样细胞（OCLs）丧失细胞外酸化功能，但保留细胞内溶酶体质子泵活性。Atp6i⁻/⁻肝脏溶酶体中的pH值以及Atp6i⁻/⁻肾脏微粒体中的质子转运与野生型小鼠相同。Atp6i⁻/⁻小鼠在血液和尿液中表现出正常的酸碱平衡。我们的结果表明，Atp6i对于破骨细胞介导的细胞外酸化是独特且必需的。