Of mothers and myelin: Aberrant myelination phenotypes in mouse model of Angelman syndrome are dependent on maternal and dietary influences.
Of mothers and myelin: Aberrant myelination phenotypes in mouse model of Angelman syndrome are dependent on maternal and dietary influences.
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DOI：
10.1016/j.bbr.2015.05.045
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发表时间：
2015-09-15
影响因子：
2.7
通讯作者：
Lagrange, Andre H.
中科院分区：
文献类型：
--
作者：
Grier, Mark D.;Carson, Robert P.;Lagrange, Andre H.
Angelman综合征（AS）是一种以发育迟缓、运动障碍和癫痫为特征的神经发育障碍。AS是由神经元中母体染色体表达的UBE 3A（一种印记基因）丢失引起的。由于Ube 3a的普遍表达和AS的破坏性，环境和母体效应的作用在很大程度上被忽视了。严重的共济失调，焦虑样行为和学习缺陷在患者和AS小鼠中有充分的记录。最近，AS患者的临床影像学研究表明髓鞘形成可能延迟或减少。利用AS的小鼠模型，我们发现皮质髓鞘蛋白的表达被破坏，其程度受母体状态的影响，因为受AS影响的母亲的AS幼崽中的异常髓鞘形成比在由未受影响的（Ube 3a（m+/p-））携带者母亲抚养的AS幼崽中观察到的异常髓鞘形成更明显。此外，喂养繁殖母亲更高的脂肪（11%对5%）饮食使这些髓鞘缺陷正常化。这些作用并不局限于髓鞘蛋白。由于AS小鼠有异常的应激反应，包括糖皮质激素受体（GR）表达的改变，我们测量了携带者和受影响的AS母亲的幼崽的GR表达。AS幼仔的GR表达高于WT同窝仔。然而，我们也发现了母体状态的影响，与未受影响的携带者母亲抚养的基因型相同的幼崽相比，受影响母亲的幼崽GR水平降低。总之，我们的研究结果表明，AS小鼠中观察到的表型可能是由独立于Ube 3a基因型的因素调制的。
Angelman Syndrome (AS) is a neurodevelopmental disorder characterized by a number of neurological problems, including developmental delay, movement disorders and epilepsy. AS results from the loss of UBE3A (an imprinted gene) expressed from the maternal chromosome in neurons. Given the ubiquitous expression of Ube3a and the devastating nature of AS, the role of environmental and maternal effects has been largely ignored. Severe ataxia, anxiety-like behaviors and learning deficits are well-documented in patients and AS mice. More recently, clinical imaging studies of AS patients suggest myelination may be delayed or reduced. Utilizing a mouse model of AS, we found disrupted expression of cortical myelin proteins, the magnitude of which is influenced by maternal status, in that the aberrant myelination in the AS pups of AS affected mothers were more pronounced than those seen in AS pups raised by unaffected (Ube3a (m+/p-)) Carrier mothers. Furthermore, feeding the breeding mothers a higher fat (11% vs 5%) diet normalizes these myelin defects. These effects are not limited to myelin proteins. Since AS mice have abnormal stress responses, including altered glucocorticoid receptor (GR) expression, we measured GR expression in pups from Carrier and affected AS mothers. AS pups had higher GR expression than their WT littermates. However, we also found an effect of maternal status, with reduced GR levels in pups from affected mothers compared to genotypically identical pups raised by unaffected Carrier mothers. Taken together, our findings suggest that the phenotypes observed in AS mice may be modulated by factors independent of Ube3a genotype.
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影响因子：
3.7
作者：
Grier MD;Carson RP;Lagrange AH
通讯作者：
Lagrange AH
DOI：
10.1073/pnas.0914805107
发表时间：
2010-04-20
影响因子：
11.1
作者：
Gleason, G.;Liu, B.;Toth, M.
通讯作者：
Toth, M.
DOI：
10.1523/jneurosci.1930-11.2013
发表时间：
2013-02-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Condon KH;Ho J;Robinson CG;Hanus C;Ehlers MD
通讯作者：
Ehlers MD
影响因子：
3.1
作者：
Harting, Inga;Seitz, Angelika;Wolf, Nicole I.
通讯作者：
Wolf, Nicole I.
影响因子：
12.7
作者：
Bradl M;Lassmann H
通讯作者：
Lassmann H