Glycine receptor mutants of the mouse: what are possible routes of inhibitory compensation?
Glycine receptor mutants of the mouse: what are possible routes of inhibitory compensation?
复制标题
小鼠的甘氨酸受体突变体：抑制补偿的可能途径是什么？
DOI：
--
复制
发表时间：
2012
影响因子：
4.8
通讯作者：
C. Villmann
中科院分区：
文献类型：
--
作者：
Natascha Schaefer;Nicolas Vogel;C. Villmann
甘氨酸能抑制的缺陷会导致人类出现复杂的神经运动障碍，称为惊跳过度 (OMIM 149400)，在啮齿类动物中具有类似的表型，其特征是惊吓反射过度和张力亢进。与人类的遗传缺陷类似，Glra1 基因以及 Glrb 基因中的单点突变、微缺失或插入也是小鼠病理学的基础。位于甘氨酸受体 (GlyR) 的 α（痉挛性、振荡性、辛辛那提、Nmf11）或 β（痉挛性）亚基中的突变在小鼠中的耐受性比在人类中低得多，这留下了人类和啮齿动物中是否存在不同的病理机制调节元件的问题。除了自发突变之外，GlyR 敲除和敲入突变体数量的不断增加也为理解神经过度兴奋或甘氨酸脑病的调节途径提供了新的见解。在过去的五年中，使用体内全细胞记录的各种努力提供了对甘氨酸能功能障碍背后的动力学参数的详细分析。这些小鼠中其他 GlyR 亚基或 GABAA 受体的突触前补偿和突触后补偿机制，以及突触外 GlyR 的作用仍然是一个有争议的问题。最近对小鼠突变振荡器的研究显示了通过独立折叠的受体结构域的互补来补偿功能的新方面。本综述重点关注小鼠甘氨酸神经传递缺陷，以人类神经过度紧张为背景讨论补偿策略。
Defects in glycinergic inhibition result in a complex neuromotor disorder in humans known as hyperekplexia (OMIM 149400) with similar phenotypes in rodents characterized by an exaggerated startle reflex and hypertonia. Analogous to genetic defects in humans single point mutations, microdeletions, or insertions in the Glra1 gene but also in the Glrb gene underlie the pathology in mice. The mutations either localized in the α (spasmodic, oscillator, cincinnati, Nmf11) or the β (spastic) subunit of the glycine receptor (GlyR) are much less tolerated in mice than in humans, leaving the question for the existence of different regulatory elements of the pathomechanisms in humans and rodents. In addition to the spontaneous mutations, new insights into understanding of the regulatory pathways in hyperekplexia or glycine encephalopathy arose from the constantly increasing number of knock-out as well as knock-in mutants of GlyRs. Over the last five years, various efforts using in vivo whole cell recordings provided a detailed analysis of the kinetic parameters underlying glycinergic dysfunction. Presynaptic compensation as well as postsynaptic compensatory mechanisms in these mice by other GlyR subunits or GABAA receptors, and the role of extra-synaptic GlyRs is still a matter of debate. A recent study on the mouse mutant oscillator displayed a novel aspect for compensation of functionality by complementation of receptor domains that fold independently. This review focuses on defects in glycinergic neurotransmission in mice discussed with the background of human hyperekplexia en route to strategies of compensation.
影响因子：
5.6
作者：
Unwin, N
通讯作者：
Unwin, N
突变小鼠痉挛中甘氨酸受体的改变。
影响因子：
64.8
作者：
White,WF;Heller,AH
通讯作者：
Heller,AH