Ultrastructural Investigation of Crystal Deposits in Npt2a Knockout Mice: Are They Similar to Human Randall's Plaques?
Ultrastructural Investigation of Crystal Deposits in Npt2a Knockout Mice: Are They Similar to Human Randall's Plaques?
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DOI：
10.1016/j.juro.2011.04.109
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发表时间：
2011-09-01
影响因子：
6.6
通讯作者：
Canales, Benjamin K.
中科院分区：
文献类型：
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作者：
Khan, Saeed R.;Canales, Benjamin K.
目的：特发性草酸钙结石可发生于肾间质磷酸钙沉积（Randall斑块）。磷酸钠协同转运蛋白（Npt 2a）缺失小鼠具有高钙尿症和高磷酸盐尿症，并产生肾小管和间质磷酸钙沉积。为了确定这只小鼠是否适合兰德尔的斑块调查，我们按时间顺序研究磷酸钙存款网站，结构和composition.Materials和方法：肾脏的Npt 2a null小鼠2天至1岁的光，扫描和透射电子显微镜检查。电子衍射和能量色散X射线微区分析，以确定矿物composition.Results：差结晶，生物磷灰石存款被视为在集合管管腔。沉积物由聚集体组成，直径约为5 μ m，呈同心组织的针状或板状微球，富含基质晶体。上皮/晶体界面充满膜结合囊泡。部分肾小管完全被晶体堵塞，晶体进入肾小管上皮细胞时偶见上皮细胞脱落。结论：磷酸钙晶体在肾小管腔内形成，并呈微球状排列。磷酸钙晶体的聚集产生晶核，晶核通过在周边添加晶体而生长。它们最终变得足够大，阻塞了肾小管腔，并清除了肾小管上皮，导致微石迁移到肾小管中。Npt 2a基因敲除小鼠间质沉积的发病机制似乎与Randall斑块的发病机制不同。由于Npt 2a敲除小鼠清除肾晶体沉积，这些小鼠可作为研究肾钙质沉着症儿童和成人晶体沉积消除的模型
Purpose: Idiopathic Ca oxalate stones may develop with attachment to renal interstitial Ca phosphate deposits (Randall's plaques). Sodium phosphate cotransporter (Npt2a) null mice have hypercalciuria and hyperphosphaturia, and produce tubular and interstitial Ca phosphate deposits. To determine whether this mouse is suitable for Randall's plaque investigations we chronologically studied Ca phosphate deposit sites, structure and composition.Materials and Methods: The kidneys of Npt2a null mice 2 days to 1 year old were examined by light, scanning and transmission electron microscopy. Electron diffraction and energy dispersive x-ray microanalyses were done to determine mineral composition.Results: Poorly crystalline, biological apatite deposits were seen in collecting duct lumina. Deposits consisted of aggregates approximately 5 mu m in diameter appearing as microspheres of concentrically organized needle or plate-like, matrix rich crystals. Epithelium/crystal interfaces were filled with membrane bound vesicles. Some tubules were completely occluded by crystals and occasionally lost the epithelium while crystals moved into the interstitium.Conclusions: Ca phosphate crystals formed in the tubular lumina and were organized as microspheres. The aggregation of Ca phosphate crystals produced nuclei, which grew by adding crystals at the periphery. They eventually became large enough to occlude the tubular lumina and obliterate the tubular epithelium, leading to the relocation of microliths into the interstitium. The pathogenesis of interstitial deposits in Npt2a null mice appears different from that proposed for Randall's plaques. Since Npt2a null mice purge the renal crystal deposits, these mice may serve as a model in which to investigate the elimination of crystal deposits in children and adults with nephrocalcinosis