Winograd C, Clayton D, Ceman S
Program in Neuroscience, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA.
Neuroscience. 2008 Nov 11;157(1):132-42. doi: 10.1016/j.neuroscience.2008.09.005. Epub 2008 Sep 9.
Individuals with fragile X syndrome (FXS) are cognitively impaired and have marked speech delays and deficits. Our goal was to characterize expression of fragile X mental retardation protein (FMRP), encoded by Fmr1 fragile X mental retardation 1 gene or transcript (FMR1), in an animal model that learns to vocalize, namely the zebra finch Taeniopygia guttata (Tgu). We cloned and sequenced the zebra finch ortholog of FMR1 (TguFmr1) and developed an antibody that recognizes TguFmrp specifically. TguFmrp has structural features similar to its human ortholog FMRP. Because FXS patients exhibit sensorimotor deficits, we examined TguFmrp expression prior to, during, and after sensorimotor song learning in zebra finches. We found that TguFmrp is expressed throughout the brain and in four major song nuclei of the male zebra finch brain, primarily in neurons. Additionally, prior to sensorimotor learning, we observed elevated TguFmrp expression in the robust nucleus of the arcopallium (RA) of post-hatch day 30 males, compared with the surrounding telencephalon, suggesting a preparation for this stage of song learning. Finally, we observed variable TguFmrp expression in the RA of adolescent and adult males: in some males it was elevated and in others it was comparable to the surrounding telencephalon. In summary, we have characterized the zebra finch ortholog of FMRP and found elevated levels in the premotor nucleus RA at a key developmental stage for vocal learning.
患有脆性X综合征（FXS）的个体存在认知障碍，且有明显的语言发育延迟和缺陷。我们的目标是在一种学会发声的动物模型——斑胸草雀Taeniopygia guttata（Tgu）中，对由Fmr1脆性X智力低下1基因或转录本（FMR1）编码的脆性X智力低下蛋白（FMRP）的表达进行表征。我们克隆并测序了斑胸草雀FMR1的直系同源基因（TguFmr1），并开发了一种能特异性识别TguFmrp的抗体。TguFmrp具有与其人类直系同源蛋白FMRP相似的结构特征。由于FXS患者表现出感觉运动缺陷，我们在斑胸草雀进行感觉运动鸣叫学习之前、期间和之后，检测了TguFmrp的表达。我们发现TguFmrp在整个大脑以及雄性斑胸草雀大脑的四个主要鸣叫核中均有表达，主要存在于神经元中。此外，在感觉运动学习之前，我们观察到与周围端脑相比，孵化后30天雄性的弓状皮质粗壮核（RA）中TguFmrp表达升高，这表明为鸣叫学习的这一阶段做了准备。最后，我们观察到青少年和成年雄性的RA中TguFmrp表达存在差异：在一些雄性中表达升高，而在另一些雄性中与周围端脑相当。总之，我们已经对FMRP的斑胸草雀直系同源基因进行了表征，并发现在发声学习的关键发育阶段，运动前核RA中的水平升高。
