Ectopic mineralization of connective tissue in Abcc6-/- mice:: effects of dietary modifications and a phosphate binder -: a preliminary study
Ectopic mineralization of connective tissue in Abcc6-/- mice:: effects of dietary modifications and a phosphate binder -: a preliminary study
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DOI：
10.1111/j.1600-0625.2007.00645.x
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发表时间：
2008-03-01
影响因子：
3.6
通讯作者：
Uitto, Jouni
中科院分区：
文献类型：
--
作者：
LaRusso, Jennifer;Jiang, Qiujie;Uitto, Jouni
弹性假黄瘤（PXE）是一种遗传性多系统疾病，由ABCC 6基因突变引起。我们通过靶向灭活相应的小鼠基因，建立了一种PXE小鼠模型。该小鼠模型的一个特征是触须球周围结缔组织囊的异位矿化。本研究旨在研究膳食盐酸司维拉姆（Renagel（R））（一种磷结合剂）和特定矿物质修饰对Abcc 6（-/-）小鼠结缔组织异位矿化的影响。向三组动物喂食特定饲料：（i）标准啮齿动物饲料，（ii）补充盐酸司维拉姆的标准啮齿动物饲料，和（iii）特定矿物质改良（高磷、低钙和低镁）的定制实验饲料。在苏木精-伊红染色的切片中使用计算机化形态测定分析和通过化学测定来测量触须的钙和磷含量来确定矿化程度。结果表明，与喂食标准饮食的对照小鼠相比，喂食标准饮食或具有矿物质修饰的饮食的Abcc 6（-/-）小鼠的矿化增加。然而，与正常饮食喂养的小鼠相比，用补充有盐酸司维拉姆的饮食喂养Abcc 6（-/-）小鼠并未改善矿化。总的来说，这些结果表明，在PXE矿化过程中可能会加剧矿物质摄入量的变化。膳食矿物质的作用，特别是磷，以及磷结合剂，在异位矿化的PXE，值得进一步研究。
Pseudoxanthoma elasticum (PXE), a heritable multisystem disorder, is caused by mutations in the ABCC6 gene. We have developed a murine model for PXE by targeted inactivation of the corresponding mouse gene. A feature of this mouse model is ectopic mineralization of connective tissue capsule surrounding the bulb of vibrissae. This study was designed to investigate the effect of dietary sevelamer hydrochloride (Renagel(R)), a phosphate binder, and specific mineral modifications on ectopic mineralization of connective tissue in Abcc6(-/-) mice. Three groups were fed a specific diet: (i) a standard rodent diet, (ii) a standard rodent diet supplemented with sevelamer hydrochloride, and (iii) a custom experimental diet with specific mineral modifications (high phosphorus, low calcium and low magnesium). The degree of mineralization was determined in hematoxylin-eosin-stained sections using computerized morphometric analysis and by chemical assays to measure the calcium and phosphorus content of the vibrissae. The results indicated increased mineralization in the Abcc6(-/-) mice fed a standard diet or a diet with mineral modifications as compared with control mice fed a standard diet. However, feeding Abcc6(-/-) mice with diet supplemented with sevelamer hydrochloride did not improve mineralization, in comparison to mice fed with normal diet. Collectively, these results suggest that the mineralization process in PXE may be exacerbated by changes in mineral intake. The role of dietary minerals, and phosphorus in particular, as well as that of phosphate binders, in ectopic mineralization of PXE, merits further investigation.