Impaired fear response in mice lacking GIT1.

Impaired fear response in mice lacking GIT1.
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DOI:
10.1016/j.neulet.2009.04.037
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发表时间:
2009-07-17
影响因子:
2.5
通讯作者:
Premont RT
Premont RT
中科院分区:
医学4区
文献类型:
--
作者:
Schmalzigaug R;Rodriguiz RM;Bonner PE;Davidson CE;Wetsel WC;Premont RT

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G 蛋白偶联受体激酶相互作用蛋白 1 (GIT1) 属于 Arf GAP 蛋白家族,参与 G 蛋白偶联受体 (GPCR) 隔离、细胞迁移、突触形成和神经元树突棘形态发生的调节。为了将 GIT1 的细胞研究扩展到体内系统,我们通过将携带条件性 Git1flox 等位基因的小鼠与表达 CMV-Cre 转基因的小鼠交配,产生了 Git1 基因全局失活的小鼠。尽管许多 GIT1 敲除 (GIT1-KO) 动物在出生后不久就死亡,但在产后早期存活下来的纯合突变体正常发育至成年并具有生育能力。成年 GIT1-KO 小鼠的行为分析显示出正常的探索、焦虑和抑郁样行为。然而,GIT1-KO 小鼠对恐惧调节和恐惧增强惊吓的反应受损。总的来说,这些发现表明 GIT1 参与了杏仁核介导的基于经验的情绪行为的调节。
G protein-coupled receptor kinase interacting protein 1 (GIT1) belongs to the family of Arf GAP proteins, and has been implicated in the regulation of G protein coupled receptor (GPCR) sequestration, cell migration, synapse formation and dendritic spine morphogenesis in neurons. To extend these cellular studies on GIT1 to an in vivo system, we generated mice with globally inactivated Git1 gene by breeding mice carrying a conditional Git1flox allele with mice expressing the CMV-Cre transgene. Although many GIT1 knockout (GIT1-KO) animals died shortly after birth, homozygous mutants that survived the early post-partum period developed normally into adulthood and were fertile. Behavioral analyses of adult GIT1-KO mice revealed normal exploratory, anxiety- and depressive-like behaviors. However, GIT1-KO mice show impaired responses to fear conditioning and fear-potentiated startle. Overall, these findings suggest that GIT1 is involved in the regulation of amygdala-mediated experience-based emotional behaviors.
DOI: 10.1074/jbc.m703298200
发表时间: 2007-07-20
影响因子: 4.8
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Kreis, Patricia;Thévenot, Emmanuel;Barnier, Jean-Vianney
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发表时间: 1993-08-01
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发表时间: 2009-02-20
影响因子: 2.5
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发表时间: 2006-05-03
期刊: EMBO JOURNAL
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发表时间: 1998-01-01
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