University of Málaga, Department of Cell Biology, Genetics, and Physiology, Málaga, Spain.
J Comp Neurol. 2011 Sep 1;519(13):2622-36. doi: 10.1002/cne.22643.
Fragile X syndrome (FXS), the most prevalent form of inherited mental retardation, is caused by the lack of FMRP (fragile mental retardation protein) as a result of the transcriptional silencing of the FMR1 gene. Here we analyze the immunohistochemical expression of the calbindin D28K protein in the hippocampus of Fmr1 knockout (KO) mice and compare it with that of their wildtype (WT) littermates. The spatial distribution pattern of calbindin-immunoreactive cells in the hippocampus was similar in WT and KO mice but for each age studied (ranging from 3.5-8 months) the dentate gyrus of Fmr1-KO mice showed a significant reduction in calbindin-immunoreactive granule cells. Also, the number of calbindin-immunoreactive cells was reduced in the CA1 pyramidal layer in KO mice compared to their WT littermates. In addition, Frm1-KO mice showed a group of calbindin-immunoreactive cells located only in the left CA3b subregion that was only sometimes observed in WT mice. Overall, the absence of FMRP results in a dysregulation of the calbindin protein expression in the hippocampus. This dysregulation is cell type- and time-dependent and as a consequence key elements of the hippocampal trisynaptic circuitry may lack calbindin in critical periods for normal memory/learning abilities to be achieved and may explain some of the FXS symptoms observed in the Fmr1-KO mouse model.
脆性 X 综合征（FXS）是最常见的遗传性智力障碍形式，是由于 FMR1 基因的转录沉默导致缺乏 FMRP（脆性智力障碍蛋白）引起的。在这里，我们分析了 Fmr1 敲除（KO）小鼠海马体中钙结合蛋白 D28K 蛋白的免疫组织化学表达，并将其与野生型（WT）同窝仔鼠进行比较。WT 和 KO 小鼠海马体中钙结合蛋白免疫反应细胞的空间分布模式相似，但在研究的每个年龄段（3.5-8 个月），Fmr1-KO 小鼠的齿状回中钙结合蛋白免疫反应颗粒细胞均显著减少。此外，与 WT 同窝仔鼠相比，KO 小鼠 CA1 锥体层中的钙结合蛋白免疫反应细胞数量减少。此外，Fm1-KO 小鼠表现出一组仅位于左侧 CA3b 亚区的钙结合蛋白免疫反应细胞，而在 WT 小鼠中仅偶尔观察到这种情况。总的来说，FMRP 的缺失导致海马体中钙结合蛋白表达失调。这种失调具有细胞类型和时间依赖性，因此，海马体三突触回路的关键元件可能在正常记忆/学习能力得以实现的关键时期缺乏钙结合蛋白，这可以解释在 Fmr1-KO 小鼠模型中观察到的一些 FXS 症状。
