Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies.
Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies.
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早期生长反应 2 基因 (EGR2) 突变的功能后果与人类髓鞘病的严重程度相关。
DOI：
10.1093/hmg/8.7.1245
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发表时间：
1999
影响因子：
3.5
通讯作者：
Lupski,JR
中科院分区：
文献类型：
--
作者：
Warner,LE;Svaren,J;Milbrandt,J;Lupski,JR
早期生长反应 2 基因 (EGR2) 是一种 Cys2His2 锌指转录因子，被认为在调节周围神经系统髓鞘形成中发挥作用。这一想法部分基于纯合 Krox20(Egr2) 敲除小鼠的表型，该小鼠在分化的早期阶段表现出 PNS 髓鞘形成不足和雪旺细胞块。最近发现人类EGR2基因突变与遗传性周围神经病Charcot-Marie-Tooth 1型、Dejerine-Sottas综合征和先天性髓鞘形成不足神经病有关。四个 EGR2 突变中的三个是显性突变，发生在锌指 DNA 结合域内。第四个突变是隐性突变，影响结合 NAB 转录共阻遏物的抑制域 (R1)。 DNA结合分析和转录分析相结合被用来确定这些突变的功能后果。锌指突变影响 DNA 结合，残留结合量与疾病严重程度直接相关。 R1 结构域突变可防止 EGR2 与 NAB 共阻遏物相互作用，从而增加转录活性。这些数据提供了对EGR2突变可能的疾病机制以及不同严重程度和遗传模式差异的原因的深入了解。
The early growth response 2 gene (EGR2) is a Cys2His2zinc finger transcription factor which is thought to play a role in the regulation of peripheral nervous system myelination. This idea is based partly on the phenotype of homozygousKrox20(Egr2) knockout mice, which display hypomyelination of the PNS and a block of Schwann cells at an early stage of differentiation. Mutations in the humanEGR2gene have recently been associated with the inherited peripheral neuropathies Charcot-Marie-Tooth type 1, Dejerine-Sottas syndrome and congenital hypomyelinating neuropathy. Three of the fourEGR2mutations are dominant and occur within the zinc finger DNA-binding domain. The fourth mutation is recessive and affects the inhibitory domain (R1) that binds the NAB transcriptional co-repressors. A combination of DNA-binding assays and transcriptional analysis was used to determine the functional consequences of these mutations. The zinc finger mutations affect DNA binding and the amount of residual binding directly correlates with disease severity. The R1 domain mutation prevents interaction of EGR2 with the NAB co-repressors and thereby increases transcriptional activity. These data provide insight into the possible disease mechanisms underlyingEGR2mutations and the reason for varying severity and differences in inheritance patterns.
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先天性髓鞘形成不足的神经病。
影响因子：
11
作者：
Y. Harati;I. Butler
通讯作者：
I. Butler
Krox-20 突变小鼠的骨形成缺陷。
影响因子：
4.6
作者：
G. Levi;P. Topilko;S. Schneider;Marco Lasagna;S. Mantero;R. Cancedda;P. Charnay
通讯作者：
P. Charnay
Krox-20 控制发育中的有髓鞘雪旺细胞的 SCIP 表达、细胞周期退出和细胞凋亡的易感性。
影响因子：
4.6
作者：
T. Zorick;D. Syroid;Adrienne M. Brown;Tom Gridley;G. Lemke
通讯作者：
G. Lemke
DOI：
10.1016/s0021-9258(18)42029-7
发表时间：
1992-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. E. Paulsen;C. Weaver;T. Fahrner;Jeffrey Milbrandt
通讯作者：
R. E. Paulsen;C. Weaver;T. Fahrner;Jeffrey Milbrandt
影响因子：
2.8
作者：
Myung, Eun;Park, Young-Lan;Joo, Young-Eun
通讯作者：
Joo, Young-Eun