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首页> 外文期刊>The European Journal of Neuroscience >Behavioural effects of extracellular matrix protein Fras1 depletion in the mouse
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Behavioural effects of extracellular matrix protein Fras1 depletion in the mouse

机译：细胞外基质蛋白FRAS1耗尽在小鼠中的行为效应

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Fras1 is an extracellular protein of the basement membranes that surround embryonic epithelia, choroid plexuses and meninges in foetal mouse brain. Depletion of Fras1 in knockout mice results in sub-epidermal blistering and fusion of eyelids and digits as well as malformation of lungs and kidneys. Mutations in the human counterpart FRAS1 are responsible for the Fraser Syndrome with clinical manifestations similar to the murine phenotype. In addition, brain deformities or mental impairments have occasionally been reported in patients with Fraser Syndrome. In the present study, we explored the possible involvement of Fras1 in brain function, analysing its expression pattern in mouse brain and investigating aspects of Frasl~'~ mice behaviour, related to the function of brain regions expressing Fras1. Transcripts were detected in choroid plexuses and in certain brain regions including cortical, hippocampal and amygdalar areas in juvenile mice. Behavioural tests revealed that Frasl~'~ mice exhibit impaired egocentric spatial memory, aberrant olfactory learning and memory, markedly reduced fear memory in an auditory fear conditioning task, as well as reduced anxiety expression in open field and elevated plus maze tests. Moreover, the extracellular matrix organization has been severely affected in cortical and subcorti-cal areas as demonstrated by Wisteria floribunda agglutinin immunolabelling. The widespread detection of Fras1 transcripts in the brain of both pre- and postnatal mice, as well as the behavioural and cellular disturbances exhibited by Frasl~'~ adult mice provide evidence for the involvement of Fras1 in brain organization and function.
机译：Fras1是胚胎小鼠大脑中围绕胚胎上皮、脉络丛和脑膜的基底膜细胞外蛋白。基因敲除小鼠体内Fras1的缺失导致表皮下起泡、眼睑和手指融合以及肺和肾畸形。人类对应物FRAS1的突变导致临床表现类似于小鼠表型的弗雷泽综合征。此外，弗雷泽综合征患者偶尔会出现脑畸形或精神障碍。在本研究中，我们探讨了Fras1可能参与大脑功能，分析了其在小鼠大脑中的表达模式，并研究了与表达Fras1的大脑区域功能相关的Frasl~'~小鼠行为方面。在幼年小鼠的脉络丛和某些大脑区域，包括皮质、海马和杏仁核区域，检测到转录物。行为测试显示，Frasl~'~小鼠的自我中心空间记忆受损，嗅觉学习和记忆异常，在听觉恐惧调节任务中的恐惧记忆显著降低，以及在开阔场地和高架+迷宫测试中焦虑表达降低。此外，紫藤凝集素免疫标记显示，皮质和皮质下区域的细胞外基质组织受到严重影响。Fras1转录本在出生前和出生后小鼠大脑中的广泛检测，以及Frasl~'~成年小鼠表现出的行为和细胞紊乱，为Fras1参与大脑组织和功能提供了证据。

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