Reduced expression of the Sp4 gene in mice causes deficits in sensorimotor gating and memory associated with hippocampal vacuolization
Reduced expression of the Sp4 gene in mice causes deficits in sensorimotor gating and memory associated with hippocampal vacuolization
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DOI：
10.1038/sj.mp.4001621
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发表时间：
2005-04-01
影响因子：
11
通讯作者：
Chien, KR
中科院分区：
文献类型：
--
作者：
Zhou, X;Long, JM;Chien, KR
Hf-1b/Sp 4是转录因子Sp1家族的成员，在发育中的神经系统中限制性表达，并且在小鼠的成年海马中最丰富。在这里，我们报告的代亚纯型Sp 4等位基因小鼠，其中的Sp 4缺陷可以通过Cre重组酶的表达获救。在突变型Sp 4缺陷小鼠的海马灰质中检测到海马苷化。Sp 4突变体的表达分析显示，齿状颗粒细胞中神经营养因子-3的表达呈年龄依赖性下降。低形态Sp 4突变小鼠在感觉运动门控和背景记忆中表现出强烈的缺陷。通过Cre依赖的拯救策略，Sp 4表达的恢复完全拯救了所有观察到的分子、组织学和行为异常。因此，我们的研究揭示了一种新的Sp 4通路，它对海马的完整性至关重要，并调节与精神疾病相关的行为过程。
Hf-1b/Sp4, a member of the Sp1 family of transcription factors, is expressed restrictively in the developing nervous system and most abundantly in adult hippocampus in mice. Here, we report the generation of hypomorphic Sp4 allele mice, in which the Sp4 deficiency can be rescued by the expression of Cre recombinase. Vacuolization was detected in the hippocampal gray matter of the mutant Sp4-deficient mice. Expression analysis of Sp4 mutant hippocampi revealed an age-dependent decrease in neurotrophin-3 expression in the dentate granule cells. Hypomorphic Sp4 mutant mice displayed robust deficits in both sensorimotor gating and contextual memory. The restoration of Sp4 expression, via a Cre-dependent rescue strategy, completely rescued all the observed molecular, histological and behavioral abnormalities. Our studies thus reveal a novel Sp4 pathway that is essential for hippocampal integrity and modulates behavioral processes relevant to psychiatric disorders.