Late Onset Neuropathy with Spontaneous Clinical Remission in Mice Lacking the POZ Domain of the Transcription Factor Myc-interacting Zinc Finger Protein 1 (Miz1) in Schwann Cells*
Late Onset Neuropathy with Spontaneous Clinical Remission in Mice Lacking the POZ Domain of the Transcription Factor Myc-interacting Zinc Finger Protein 1 (Miz1) in Schwann Cells*
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雪旺细胞中缺乏转录因子 Myc 相互作用锌指蛋白 1 (Miz1) POZ 结构域的小鼠迟发性神经病并可自发临床缓解*
DOI：
10.1074/jbc.m114.605931
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Elsässer
中科院分区：
文献类型：
--
作者：
Sanz-Moreno;Fuhrmann;Zankel;Reingruber;Meijer;Niemann;Elsässer
转录因子Miz 1（Myc相互作用锌指1）是已知的细胞周期调节因子，但也具有不依赖于细胞周期的功能。在这里，我们分析了Miz 1在周围神经系统中的作用，使用早期胚胎条件性敲除模型，其中Miz 1 POZ结构域在雪旺细胞中被消融。尽管有髓神经纤维的发育没有受损，但Miz 1 Δ POZ小鼠在3个月大时获得了周围神经病变的行为体征。此时，坐骨神经的超微结构分析显示纤维脱髓鞘和髓鞘形成障碍，伴有大量外折和巨噬细胞局灶性浸润。虽然编码髓鞘结构蛋白的基因表达，如：神经节苷脂、髓鞘碱性蛋白和髓鞘零蛋白，与对照组相比，在Miz 1 Δ POZ小鼠中，与髓鞘形成负调控相关的基因，包括c-Jun、Sox 2和Id 2，表达上调。在4个月以上的动物中，运动障碍消失，坐骨神经的超微结构显示出许多tomacula和髓鞘再生纤维，如较薄的髓鞘所示。在1岁之前未观察到第二次急性发作。因此，在本发明中，在Schwann细胞中Miz 1 POZ结构域的缺失诱导急性神经病，随后再生，其中脱髓鞘和再髓鞘之间存在持续的平衡。Miz 1 Δ POZ小鼠在有髓鞘纤维的维持方面受损，并且是研究成人周围神经中再髓鞘形成的有希望的模型。结合转录因子Miz 1在不同的细胞和组织中具有多种功能。结论Miz 1在周围神经髓鞘稳定中起重要作用，切除雪旺细胞Miz 1功能可为周围神经病变的缓解提供新的模型。
The transcription factor Miz1 (Myc-interacting zinc finger 1) is a known regulator of the cell cycle but also has cell cycle-independent functions. Here we analyzed the role of Miz1 in the peripheral nervous system, using an early embryonic conditional knock-out model in which the Miz1 POZ domain is ablated in Schwann cells. Although the development of myelinated nerve fibers was not impaired,Miz1ΔPOZmice acquired behavioral signs of a peripheral neuropathy at the age of 3 months. At this time, ultrastructural analysis of the sciatic nerve showed de- and dysmyelination of fibers, with massive outfoldings and a focal infiltration of macrophages. Although the expression of genes encoding structural myelin proteins, such as periaxin, myelin basic protein, and myelin protein zero, was decreased, genes associated with a negative regulation of myelination, including c-Jun,Sox2, andId2, were up-regulated inMiz1ΔPOZmice compared with controls. In animals older than 4 months, the motor disabilities vanished, and the ultrastructure of the sciatic nerve exhibited numerous tomacula and remyelinated fibers, as indicated by thinner myelin. No second acute attack was observed up to the age of 1 year. Thus, the deletion of the Miz1 POZ domain in Schwann cells induces an acute neuropathy with a subsequent regeneration in which there is ongoing balancing between de- and remyelination.Miz1ΔPOZmice are impaired in the maintenance of myelinated fibers and are a promising model for studying remyelination in adult peripheral nerves.The Myc-binding transcription factor Miz1 has multiple functions in different cells and tissues.ResultsAblation of the Miz1 POZ domain in Schwann cells causes a late onset peripheral neuropathy with spontaneous remission.ConclusionMiz1 plays an essential role in myelin homeostasis of peripheral nerves.SignificanceAblation of Miz1 function in Schwann cells leads to a new model for remitting peripheral neuropathies.
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影响因子：
3.7
作者：
Sanz-Moreno A;Fuhrmann D;Wolf E;von Eyss B;Eilers M;Elsässer HP
通讯作者：
Elsässer HP
影响因子：
3.7
作者：
Hönnemann J;Sanz-Moreno A;Wolf E;Eilers M;Elsässer HP
通讯作者：
Elsässer HP
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影响因子：
2.9
作者：
D. Meller;U. Eysel;R. Schmidt
通讯作者：
R. Schmidt
影响因子：
10.5
作者：
Jan van Riggelen;Judith M. Müller;T. Otto;Vincent Beuger;Alper Yetil;P. Choi;C. Kosan;T. Möröy;D. Felsher;M. Eilers
通讯作者：
Jan van Riggelen;Judith M. Müller;T. Otto;Vincent Beuger;Alper Yetil;P. Choi;C. Kosan;T. Möröy;D. Felsher;M. Eilers
非发育病毒的轴突髓磷脂转移。
影响因子：
3.7
作者：
Roussarie JP;Ruffié C;Edgar JM;Griffiths I;Brahic M
通讯作者：
Brahic M