Postnatal and adult consequences of loss of huntingtin during development: Implications for Huntington's disease.
Postnatal and adult consequences of loss of huntingtin during development: Implications for Huntington's disease.
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DOI：
10.1016/j.nbd.2016.09.006
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发表时间：
2016-12
影响因子：
6.1
通讯作者：
Molero, Aldrin E.
中科院分区：
文献类型：
--
作者：
Arteaga-Bracho, Eduardo E.;Gulinello, Maria;Winchester, Michael L.;Pichamoorthy, Nandini;Petronglo, Jenna R.;Zambrano, Alicia D.;Inocencio, Julio;De Jesus, Chirstopher D.;Louie, Joseph O.;Gokhan, Solen;Mehler, Mark F.;Molero, Aldrin E.
关键词：
亨廷顿蛋白（mHtt）突变导致亨廷顿病（HD）小鼠模型前脑发育中的一系列损伤。这些发育改变是否是由于功能丧失或获得机制，并有助于HD发病机制尚不清楚。我们研究了发育过程中亨廷顿蛋白（Htt）功能的选择性丧失对出生后细胞死亡的脆弱性的作用。我们采用在整个胚胎期至出生后第21天（Hdhd·hyp）表达极低水平Htt的小鼠。我们证明Hdhd·hyp小鼠表现出：（1）晚年纹状体和皮质神经元变性;（2）神经和骨骼肌改变;（3）白色束损伤和轴突变性。Hdhd·hyp胚胎还表现出苍白球下异位、异常纹状体成熟和胶质细胞生成失调。这些结果表明，与Htt功能相关的发育缺陷使存在于离散神经灶的细胞对细胞死亡越来越敏感，从而暗示HD发病机制中可能存在功能丧失的发育组分。
The mutation in huntingtin (mHtt) leads to a spectrum of impairments in the developing forebrain of Huntington’s disease (HD) mouse models. Whether these developmental alterations are due to loss- or gain-of-function mechanisms and contribute to HD pathogenesis is unknown. We examined the role of selective loss of huntingtin (Htt) function during development on postnatal vulnerability to cell death. We employed mice expressing very low levels of Htt throughout embryonic life to postnatal day 21 (Hdhd•hyp). We demonstrated that Hdhd•hyp mice exhibit: (1) late-life striatal and cortical neuronal degeneration; (2) neurological and skeletal muscle alterations; and (3) white matter tract impairments and axonal degeneration. Hdhd•hyp embryos also exhibited subpallial heterotopias, aberrant striatal maturation and deregulation of gliogenesis. These results indicate that developmental deficits associated with Htt functions render cells present at discrete neural foci increasingly susceptible to cell death, thus implying the potential existence of a loss-of-function developmental component to HD pathogenesis.
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影响因子：
5.8
作者：
Gulinello M;Acquarone M;Kim JH;Spray DC;Barbosa HS;Sellers R;Tanowitz HB;Weiss LM
通讯作者：
Weiss LM
影响因子：
5.3
作者：
Halliday, GM;McRitchie, DA;McCusker, E
通讯作者：
McCusker, E
不断发展的神经胶质发生概念：回顾接下来的25年。
影响因子：
16.2
作者：
Freeman MR;Rowitch DH
通讯作者：
Rowitch DH
DOI：
10.1523/jneurosci.5473-08.2009
发表时间：
2009-02-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Graham RK;Pouladi MA;Joshi P;Lu G;Deng Y;Wu NP;Figueroa BE;Metzler M;André VM;Slow EJ;Raymond L;Friedlander R;Levine MS;Leavitt BR;Hayden MR
通讯作者：
Hayden MR
影响因子：
16.2
作者：
Godin, Juliette D.;Colombo, Kelly;Humbert, Sandrine
通讯作者：
Humbert, Sandrine