Neonatal Death in Mice Lacking Cardiotrophin-like Cytokine is Associated with Multifocal Neuronal Hypoplasia
Neonatal Death in Mice Lacking Cardiotrophin-like Cytokine is Associated with Multifocal Neuronal Hypoplasia
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DOI：
10.1354/vp.08-vp-0239-b-bc
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发表时间：
2009-05-01
影响因子：
2.4
通讯作者：
Siu, G.
中科院分区：
文献类型：
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作者：
Zou, X.;Bolon, B.;Siu, G.
具有睫状神经营养因子 (Cntf) 受体 α (Cntf-R α) 或细胞因子样因子 1 (Clf)（Cntf-II（一种异二聚体 Cntf-R α 配体）的一个组成部分）无效突变的小鼠，在新生儿时会因影响面核和腰脊髓腹角的运动神经元损失而死亡。暴露于心肌营养素样细胞因子 (Clc)（另一种假定的 Cntf-II 元件）可支持运动神经元在体外和卵内的存活。确认 Clc 消融诱导与 Clf 删除相同的表型将支持 Clc 在功能性 Cntf-II 复合体中的作用。在这项研究中，Clc基因敲除小鼠的面部运动能力下降，不能吸奶，24小时内死亡，面核和腰椎腹角的运动神经元分别减少32%和29%；因此，Clc 对于运动神经元在发育过程中的存活至关重要。 Clc 敲除表型与缺乏 Cntf-R α 或 Clf 的小鼠表型的一致性支持了 Clc 参与 Cntf-II 的假设。
Mice with null mutations of ciliary neurotrophic factor (Cntf) receptor alpha (Cntf-R alpha), or cytokine-like factor 1 (Clf), one component of Cntf-II (a heterodimeric Cntf-R alpha ligand), die as neonates from motor neuron loss affecting the facial nucleus and ventral horn of the lumbar spinal cord. Exposure to cardiotrophin-like cytokine (Clc), the other putative Cntf-II element, supports motor neuron survival in vitro and in ovo. Confirmation that Clc ablation induces an equivalent phenotype to Clf deletion would support a role for Clc in the functional Cntf-II complex. In this study, Clc knockout mice had decreased facial motility, did not suckle, died within 24 hours, and had 32% and 29% fewer motor neurons in the facial nucleus and lumbar ventral horn, respectively; thus, Clc is essential for motor neuron survival during development. The concordance of the Clc knockout phenotype with those of mice lacking Cntf-R alpha or Clf bolsters the hypothesis that Clc participates in Cntf-II.