RhoE deficiency produces postnatal lethality, profound motor deficits and neurodevelopmental delay in mice.
RhoE deficiency produces postnatal lethality, profound motor deficits and neurodevelopmental delay in mice.
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DOI：
10.1371/journal.pone.0019236
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发表时间：
2011-04-28
期刊：
影响因子：
3.7
通讯作者：
Pérez-Roger I
中科院分区：
文献类型：
--
作者：
Mocholí E;Ballester-Lurbe B;Arqué G;Poch E;Peris B;Guerri C;Dierssen M;Guasch RM;Terrado J;Pérez-Roger I
Rnd 蛋白是 Rho GTPases 的一个亚家族，参与控制肌动蛋白细胞骨架动力学和其他细胞功能，如运动、增殖和存活。与 Rho 家族的其他成员不同，Rnd 蛋白缺乏 GTP 酶活性，因此保持组成型活性。我们最近描述了 RhoE/Rnd3 在中枢神经系统中表达，并且它具有促进神经突形成的作用。尽管 Rnd 蛋白在发育过程中可能具有相关性，但其在体内的作用尚不清楚。为了深入了解 RhoE 的体内功能，我们通过外显子捕获盒培育了缺乏 RhoE 表达的小鼠。 RhoE 缺失小鼠 (RhoE gt/gt) 出生时体型较小，表现出生长迟缓和出生后早期死亡，因为只有一半的 RhoE gt/gt 小鼠在出生后第 15 天 (PD) 后存活，100% 到 PD 29 天死亡。RhoE gt/gt 小鼠在大多数神经行为测试中表现出异常的体位，伴有严重的运动障碍和表现受损。无效突变小鼠活动减退，表现出不成熟的运动模式，并且后肢成熟反应的出现显着延迟。此外，它们在钢丝悬挂、垂直攀爬和攀爬、翻正反射和负趋地性测试中的表现比对照同窝动物差。此外，RhoE 消融会导致神经肌肉成熟延迟和脊髓运动神经元数量减少。最后，RhoE gt/gt 小鼠缺乏腓总神经，因此表现出目标肌肉完全萎缩。这是第一个研究 Rnd 蛋白亚家族成员体内功能的模型，揭示了 Rnd3/RhoE 在正常发育中的重要作用，并表明该蛋白可能参与神经系统疾病。
Rnd proteins are a subfamily of Rho GTPases involved in the control of actin cytoskeleton dynamics and other cell functions such as motility, proliferation and survival. Unlike other members of the Rho family, Rnd proteins lack GTPase activity and therefore remain constitutively active. We have recently described that RhoE/Rnd3 is expressed in the Central Nervous System and that it has a role in promoting neurite formation. Despite their possible relevance during development, the role of Rnd proteins in vivo is not known. To get insight into the in vivo function of RhoE we have generated mice lacking RhoE expression by an exon trapping cassette. RhoE null mice (RhoE gt/gt) are smaller at birth, display growth retardation and early postnatal death since only half of RhoE gt/gt mice survive beyond postnatal day (PD) 15 and 100% are dead by PD 29. RhoE gt/gt mice show an abnormal body position with profound motor impairment and impaired performance in most neurobehavioral tests. Null mutant mice are hypoactive, show an immature locomotor pattern and display a significant delay in the appearance of the hindlimb mature responses. Moreover, they perform worse than the control littermates in the wire suspension, vertical climbing and clinging, righting reflex and negative geotaxis tests. Also, RhoE ablation results in a delay of neuromuscular maturation and in a reduction in the number of spinal motor neurons. Finally, RhoE gt/gt mice lack the common peroneal nerve and, consequently, show a complete atrophy of the target muscles. This is the first model to study the in vivo functions of a member of the Rnd subfamily of proteins, revealing the important role of Rnd3/RhoE in the normal development and suggesting the possible involvement of this protein in neurological disorders.
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影响因子：
64.8
作者：
Billuart, P;Bienvenu, T;Chelly, J
通讯作者：
Chelly, J
影响因子：
12.4
作者：
Fortier, M.;Comunale, F.;Gauthier-Rouviere, C.
通讯作者：
Gauthier-Rouviere, C.
影响因子：
64.8
作者：
Heng, Julian Ik-Tsen;Nguyen, Laurent;Guillemot, Francois
通讯作者：
Guillemot, Francois
影响因子：
7.5
作者：
Huang, TY;DerMardirossian, C;Bokoch, GM
通讯作者：
Bokoch, GM
影响因子：
3.5
作者：
Bi, Weimin;Yan, Jiong;Lupski, James R.
通讯作者：
Lupski, James R.