Conditional ablation of the Mat1 subunit of TFIIH in Schwann cells provides evidence that Mat1 is not required for general transcription
Conditional ablation of the Mat1 subunit of TFIIH in Schwann cells provides evidence that Mat1 is not required for general transcription
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DOI：
10.1242/jcs.00121
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发表时间：
2002-11-15
影响因子：
4
通讯作者：
Mäkelä, TP
中科院分区：
文献类型：
--
作者：
Korsisaari, N;Rossi, DJ;Mäkelä, TP
哺乳动物Mat 1蛋白作为Cdk活化激酶（CAK）的一部分参与细胞周期调控，并作为转录因子TFIIH的亚基参与转录调控。为了解决在体内的作用，我们已经使用了Cre/loxP系统有条件地消融在成人有丝分裂和有丝分裂后的谱系中的Mat 1。我们发现，有丝分裂细胞的生殖谱系迅速死亡后，破坏的MAT 1表明在这些细胞中的MAT 1的绝对需求。相比之下，有丝分裂后髓鞘形成的雪旺细胞能够在没有Mat 1的情况下获得成熟的有髓鞘表型。此外，突变动物没有表现出形态学或生理学迹象的雪旺细胞功能障碍到成年早期。然而，超过3个月的年龄，在坐骨神经中的有髓鞘的雪旺细胞获得了严重的hypomyelinating形态与变化范围从细胞变性到完全裸露的轴突。这种表型与广泛的增殖和髓鞘再生有关，我们的证据表明这是由无髓鞘雪旺细胞池进行的。这些结果表明，马特1是不是必不可少的转录程序背后的髓鞘的外周轴突的雪旺细胞，并建议在这些细胞中的RNA聚合酶II介导的转录马特1的功能是监管，而不是必不可少的。
The mammalian Mat1 protein has been implicated in cell cycle regulation as part of the Cdk activating kinase (CAK), and in regulation of transcription as a subunit of transcription factor TFIIH. To address the role of Mat1 in vivo, we have used a Cre/loxP system to conditionally ablate Mat1 in adult mitotic and post-mitotic lineages. We found that the mitotic cells of the germ lineage died rapidly upon disruption of Mat1 indicating an absolute requirement of Mat1 in these cells. By contrast, post-mitotic myelinating Schwann cells were able to attain a mature myelinated phenotype in the absence of Mat1. Moreover, mutant animals did not show morphological or physiological signs of Schwann cell dysfunction into early adulthood. Beyond 3 months of age, however, myelinated Schwann cells in the sciatic nerves acquired a severe hypomyelinating morphology with alterations ranging from cells undergoing degeneration to completely denuded axons. This phenotype was coupled to extensive proliferation and remyelination that our evidence suggests was undertaken by the non-myelinated Schwann cell pool. These results indicate that Mat1 is not essential for the transcriptional program underlying the myelination of peripheral axons by Schwann cells and suggest that the function of Mat1 in RNA polymerase II-mediated transcription in these cells is regulatory rather than essential.