Similar phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage
Similar phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage
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DOI：
10.1016/j.bbrc.2012.08.122
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发表时间：
2012-10-05
影响因子：
3.1
通讯作者：
Takahashi, Masahide
中科院分区：
文献类型：
--
作者：
Asai, Masato;Asai, Naoya;Takahashi, Masahide
Girdin 是一种 Akt 底物和肌动蛋白结合蛋白。具有 Girdin 种系缺失（非条件性基因敲除，（ncKO））的小鼠表现出出生后完全致死，并伴有生长迟缓和神经元细胞迁移缺陷，导致嗅球发育不全和齿状陀螺中的颗粒细胞分散。然而，Girdin ncKO 小鼠的生理和分子异常尚不完全清楚。在这项研究中，我们首先利用 ncKO 小鼠组织中的 β-半乳糖苷酶活性定义了 Girdin 在新生儿 (P1) 和成人（6 个月或以上）中的分布。结果表明，Girdin 在整个神经系统（脑、脊髓、肠和自主神经系统）中表达。此外，在非神经组织中检测到β-半乳糖苷酶活性，特别是在具有高张力的组织中，例如肌腱、心脏瓣膜和骨骼肌。为了鉴定Girdin ncKO表型起源的细胞群，将新产生的Girdin Fox小鼠与巢蛋白启动子驱动的Cre转基因小鼠杂交以获得Girdin条件敲除（cKO）小鼠。 Girdin cKO 小鼠的表型与 ncKO 小鼠几乎相同，包括出生后致死率、生长迟缓和神经元迁移减少。我们的研究结果表明，巢蛋白细胞谱系中 Girdin 的缺失是 Girdin ncKO 小鼠表型的基础。 (C) 2012 Elsevier Inc. 保留所有权利。
Girdin is an Akt substrate and actin-binding protein. Mice with germ-line deletions of Girdin (a non-conditional knockout, (ncKO)) exhibit complete postnatal lethality accompanied by growth retardation and neuronal cell migration defects, which results in hypoplasia of the olfactory bulb and granule cell dispersion in the dentate gyros. However, the physiological and molecular abnormalities in Girdin ncKO mice are not fully understood. In this study, we first defined the distribution of Girdin in neonates (P1) and adults (6 months or older) using beta-galactosidase activity in tissues from ncKO mice. The results indicate that Girdin is expressed throughout the nervous system (brain, spinal cord, enteric and autonomic nervous systems). In addition, beta-galactosidase activity was detected in non-neural tissues, particularly in tissues with high tensile force, such as tendons, heart valves, and skeletal muscle. In order to identify the cellular population where the Girdin ncKO phenotype originates, newly generated Girdin fox mice were crossed with nestin promoter-driven Cre transgenic mice to obtain Girdin conditional knockout (cKO) mice. The phenotype of Girdin cKO mice was almost identical to ncKO mice, including postnatal lethality, growth retardation and decreased neuronal migration. Our findings indicate that loss of Girdin in the nestin cell lineage underlies the phenotype of Girdin ncKO mice. (C) 2012 Elsevier Inc. All rights reserved.