Loss of the NHE2 Na+/H+ exchanger has no apparent effect on diarrheal state of NHE3-deficient mice
Loss of the NHE2 Na+/H+ exchanger has no apparent effect on diarrheal state of NHE3-deficient mice
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DOI：
10.1152/ajpgi.2001.281.6.g1385
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发表时间：
2001-12-01
影响因子：
4.5
通讯作者：
Shull, GE
中科院分区：
文献类型：
--
作者：
Ledoussal, C;Woo, AL;Shull, GE
NHE2 和 NHE3 在肠刷状缘膜上的表达表明 Na+/H+ 交换器均具有吸收功能。对基因敲除小鼠的研究表明，NHE3 的缺失而非 NHE2 会导致腹泻，这证明 NHE3 是主要的吸收交换器，并表明 NHE2 贡献的任何剩余吸收能力不足以完全补偿 NHE3 的缺失。为了检验NHE2对NHE3缺陷小鼠的腹泻状态提供部分补偿的假设，我们将携带Nhe2和Nhe3基因无效突变的双杂合小鼠进行杂交，并分析了它们后代的表型。 NHE3缺陷小鼠中NHE2的额外损失没有导致生存能力明显下降，没有进一步损害全身酸碱状态或醛固酮水平增加，并且没有明显恶化腹泻状态。这些吸收缺陷的体内表型相关性表明，依赖于顶端 Na+/H+ 交换的 NaCl、HCO3- 和液体吸收绝大多数是由于 NHE3 的活性，而 NHE2 的贡献很小。
The expression of NHE2 and NHE3 on intestinal-brush border membranes suggests that both Na+/H+ exchangers serve absorptive functions. Studies with knockout mice showed that the loss of NHE3, but not NHE2, causes diarrhea, demonstrating that NHE3 is the major absorptive exchanger and indicating that any remaining absorptive capacity contributed by NHE2 is not sufficient to compensate fully for the loss of NHE3. To test the hypothesis that NHE2 provides partial compensation for the diarrheal state of NHE3-deficient mice, we crossed doubly heterozygous mice carrying null mutations in the Nhe2 and Nhe3 genes and analyzed the phenotypes of their offspring. The additional loss of NHE2 in NHE3-deficient mice caused no apparent reduction in viability, no further impairment of systemic acid-base status or increase in aldosterone levels, and no apparent worsening of the diarrheal state. These in vivo phenotypic correlates of the absorptive defect suggest that the NaCl, HCO3-, and fluid absorption that is dependent on apical Na+/H+ exchange is due overwhelmingly to the activity of NHE3, with little contribution from NHE2.