Intestinal Depletion of NaPi-IIb/Slc34a2 in Mice: Renal and Hormonal Adaptation
Intestinal Depletion of NaPi-IIb/Slc34a2 in Mice: Renal and Hormonal Adaptation
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DOI：
10.1002/jbmr.2523
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发表时间：
2015-10-01
影响因子：
6.2
通讯作者：
Biber, Juerg
中科院分区：
文献类型：
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作者：
Hernando, Nati;Myakala, Komuraiah;Biber, Juerg
Na+依赖性磷酸盐共转运体NaPi-IIb （SLC34A2）广泛表达，在mRNA丰度最高的器官中，肠、肺和睾丸均有表达。在小鼠肠道中，NaPi-IIb的表达仅限于回肠，其中共转运蛋白特异性定位于刷状边界膜（BBM）并介导无机磷酸盐（Pi）的主动运输。完全消融NaPi-IIb是胚胎致死性的，而在年轻小鼠中，转运体的整体但可诱导去除会导致肠道Pi丢失和肺部钙化。在这里，我们报告了一个组成性但肠道特异性的NaPi-IIb/ slc34a2缺陷小鼠模型的产生。NaPi-IIb本构性肠道消融术可产生正常生长的活仔。纯合子小鼠的特点是粪便中Pi的浪费和从回肠分离的BBM囊泡（BBMVs）中Na/Pi共运输活性完全缺失。相比之下，这些动物的尿中Pi的排泄减少了。野生型和napi - iib缺乏小鼠的血浆Pi水平相似。在女性中，减少的磷酸尿与肾BBMVs中更高的NaPi-IIa表达和更高的Na/Pi共转运活性以及血浆中完整FGF-23水平的降低有关。在男性中也发现了类似的趋势。因此，NaPi-IIb是小鼠回肠中唯一的腔内Na+依赖性Pi转运体，其缺失在成年雌性中通过涉及骨肾轴的机制得到充分补偿。这种机制对成年男性适应性反应的贡献不太明显。(C) 2015年美国骨与矿物研究学会。
The Na+-dependent phosphate-cotransporter NaPi-IIb (SLC34A2) is widely expressed, with intestine, lung, and testis among the organs with highest levels of mRNA abundance. In mice, the intestinal expression of NaPi-IIb is restricted to the ileum, where the cotransporter localizes specifically at the brush border membrane (BBM) and mediates the active transport of inorganic phosphate (Pi). Constitutive full ablation of NaPi-IIb is embryonically lethal whereas the global but inducible removal of the transporter in young mice leads to intestinal loss of Pi and lung calcifications. Here we report the generation of a constitutive but intestinal-specific NaPi-IIb/Slc34a2-deficient mouse model. Constitutive intestinal ablation of NaPi-IIb results in viable pups with normal growth. Homozygous mice are characterized by fecal wasting of Pi and complete absence of Na/Pi cotransport activity in BBM vesicles (BBMVs) isolated from ileum. In contrast, the urinary excretion of Pi is reduced in these animals. The plasma levels of Pi are similar in wild-type and NaPi-IIb-deficient mice. In females, the reduced phosphaturia associates with higher expression of NaPi-IIa and higher Na/Pi cotransport activity in renal BBMVs, as well as with reduced plasma levels of intact FGF-23. A similar trend is found in males. Thus, NaPi-IIb is the only luminal Na+-dependent Pi transporter in the murine ileum and its absence is fully compensated for in adult females by a mechanism involving the bone-kidney axis. The contribution of this mechanism to the adaptive response is less apparent in adult males. (C) 2015 American Society for Bone and Mineral Research.