Lack of nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2): consequences for mouse bladder development and function.
Lack of nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2): consequences for mouse bladder development and function.
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DOI：
10.1002/nau.22372
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发表时间：
2013-11
影响因子：
2
通讯作者：
Andersson KE
中科院分区：
文献类型：
--
作者：
Hicks AN;Campeau L;Burmeister D;Bishop CE;Andersson KE
描述当烟酰胺单核苷酸腺基转移酶2(Nmnat2)缺失或减少时，对膀胱发育和功能的形态和功能影响。缺乏Nmnat2的膀胱肿胀(BLAD)小鼠和杂合子被用于本研究。用免疫组织化学方法研究膀胱的形态和发育，包括尿路上皮、平滑肌和神经标志物。通过脏器沐浴实验和膀胱测压评价其功能效应。纯合子突变体畸形并在出生时死亡，而杂合子存活下来，形态上与野生型对照没有什么不同。BLAD突变体在胚胎15.5天(E15.5)就出现了形态上的膀胱变化，在E18.5天出现了极度膨胀的膀胱。免疫组织化学染色显示，三种基因型的膀胱层均有成熟标志的表达。免疫组织化学染色未见BLAD突变型膀胱内神经分布。器官浴分析表明，Blad突变体的膀胱对氨基甲胆碱表现出失神经过敏的迹象，而对电刺激神经在E18.5处没有反应。与野生型对照相比，在E18.5处Nmnat2表达降低的成年杂合子对氨基甲胆碱和电刺激的反应降低。后者也保留了排空膀胱的能力，但与对照组相比，他们的排尿压力增加了。完全失去Nmnat2会导致成熟但在子宫内扩张的膀胱，与生存不相容。Nmnat2的适度缺失对膀胱的发育和存活率没有影响，对以后的生活中的膀胱功能只有轻微的影响。
To describe the morphological and functional consequences for bladder development and function when nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) is lacking or reduced. The Bloated Bladder (Blad) mouse, lacking Nmnat2, and heterozygotes were utilized for this investigation. Morphology and development of the bladder were studied using immunohistochemistry against urothelial, smooth muscle, and nerve markers. Functional effects were assessed by organ bath experiments and cystometry. Homozygote mutants were malformed and died at birth, whereas heterozygotes survived and morphologically did not differ from wild-type controls. Morphological bladder changes appeared in the Blad mutants as early as embryonic day 15.5 (E15.5) with an extremely distended bladder at E18.5. Staining revealed that all the bladder layers were present and expressed mature markers in all three genotypes. No nerves could be demonstrated by immunohistochemistry in the Blad mutant bladder at E18.5. Organ bath analysis showed that bladders from Blad mutant showed signs of denervation supersensitivity in response to carbachol, and no response to electrical stimulation of nerves at E18.5. Adult heterozygotes, which have a reduced expression of Nmnat2 at E18.5, showed decreased responses to carbachol and electrical stimulation compared to wild-type controls. The latter also retained their ability to empty their bladders, but showed increased micturition pressures compared to controls. Complete loss of Nmnat2 leads to a mature but distended bladder in utero and is not compatible with survival. Moderate loss of Nmnat2 has no effect on bladder development, survival, and has only modest effects on bladder function later in life.
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影响因子：
4.8
作者：
Mayer, Paul R.;Huang, Nian;Yu, Gang
通讯作者：
Yu, Gang
影响因子：
2.9
作者：
Shiroyanagi, Yoshiyuki;Liu, Benchun;Baskin, Laurence S.
通讯作者：
Baskin, Laurence S.
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影响因子：
3.7
作者：
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通讯作者：
Bishop CE
影响因子：
3.5
作者：
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通讯作者：
Lu, Hui-Chen
影响因子：
4.6
作者：
Wang, Baiping;Harrison, Wilbur;Zheng, Hui
通讯作者：
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