Pitt-Hopkins Mouse Model has Altered Particular Gastrointestinal Transits In Vivo.
Pitt-Hopkins Mouse Model has Altered Particular Gastrointestinal Transits In Vivo.
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DOI：
10.1002/aur.1467
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Parpura V
中科院分区：
文献类型：
--
作者：
Grubišić V;Kennedy AJ;Sweatt JD;Parpura V
皮特-霍普金斯综合征（PTHS）是一种神经发育障碍，被归类为自闭症谱系障碍，由转录因子4（TCF 4）的单倍不足引起。PTHS患者最常见的非神经症状是胃肠道（GI）紊乱，主要是胃食管反流和严重便秘（分别约占PTHS患者的30%和75%）。我们假设最近认识到的PTHS小鼠模型将表现出肠道功能的问题。我们对15- 19周龄的雄性小鼠进行了一系列体内试验，这些小鼠是TCF 4功能缺失的杂合子，模拟PTHS患者的TCF 4单倍不足，以及它们的野生型同窝出生小鼠。数据收集和初始分析均采用盲法，即计算每只动物的平均值后收到基因分型密钥，然后计算各组的平均值/中位数。各组之间的体重、粪粒排出量和液体含量相似，表明PTHS小鼠的总体生长正常，其总体生理GI运动和肠道分泌/吸收正常。肠道长度和大体外观无显著差异，表明PTHS小鼠在大体解剖学方面具有正常肠道。然而，对肠道传输的评估表明，虽然各组之间的全肠道传输速度相似，但PTHS小鼠的上GI和远端结肠传输速度显著降低。这是PTHS小鼠中特定肠道相关问题的第一个证据。我们的研究也验证了TCF 4功能敲除小鼠作为研究PTHS相关胃肠道紊乱的动物模型。
Pitt–Hopkins syndrome (PTHS) is a neurodevelopmental disorder, classified as an autism spectrum disorder that is caused by the haploinsufficiency of Transcription Factor 4 (TCF4). The most common non-neurological symptoms in PTHS patients are gastrointestinal (GI) disturbances, mainly gastroesophageal reflux and severe constipation (in about 30 and 75% of PTHS patients, respectively). We hypothesized that the recently recognized mouse model of PTHS will exhibit problems with their gut function. We conducted series of in vivo tests on 15- to 19- week old male mice, heterozygous for the TCF4 functional deletion, mimicking the TCF4 haploinsufficiency in PTHS patients, and their wild type littermates. Data collection and initial analysis were performed blindly, that is, the genotyping key was received after the mean values were calculated for each individual animal, and then mean/median of each group was subsequently calculated. Body weight, fecal pellet output, and fluid content were similar between the groups, indicating normal gross growth of PTHS mice and their overall physiological GI motility and intestinal secretion/absorption. There were no significant differences in gut length and gross appearance pointing out that PTHS mice have normal gut in gross anatomical terms. However, the assessment of gut transit indicates that, while whole-gut transit velocity was similar between the groups, the upper GI and distal colon transit velocities were significantly reduced in the PTHS mice. This is the first evidence of specific gut related problems in the PTHS mice. Our study also validates the TCF4 functional knockout mice as an animal model to study PTHS-associated GI disturbances.
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影响因子：
3.7
作者：
Forrest MP;Waite AJ;Martin-Rendon E;Blake DJ
通讯作者：
Blake DJ
影响因子：
12.8
作者：
Sweatt, J. David
通讯作者：
Sweatt, J. David
影响因子：
29.4
作者：
McClain J;Grubišić V;Fried D;Gomez-Suarez RA;Leinninger GM;Sévigny J;Parpura V;Gulbransen BD
通讯作者：
Gulbransen BD
影响因子：
3.9
作者：
Whalen, Sandra;Heron, Delphine;Giurgea, Irina
通讯作者：
Giurgea, Irina
DOI：
10.1073/pnas.0707456104
发表时间：
2007-09-25
影响因子：
11.1
作者：
Flora, Adriano;Garcia, Jesus J.;Zoghbi, Huda Y.
通讯作者：
Zoghbi, Huda Y.