Behavioural Neuroscience Section, Department of Cell Biology & Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
PLoS One. 2013 May 21;8(5):e64407. doi: 10.1371/journal.pone.0064407. Print 2013.
Reelin is a large secreted extracellular matrix glycoprotein playing an important role in early neurodevelopment. Several genetic studies found an association between RELN gene and increased risk of autism suggesting that reelin deficiency may be a vulnerability factor in its etiology. Moreover, a reduced reelin expression has been observed in several brain regions of subjects with Autism Spectrum Disorders. Since a number of reports have documented presence of vocal and neuromotor abnormalities in patients with autism and suggested that these dysfunctions predate the onset of the syndrome, we performed a fine-grain characterization of the neonatal vocal and motor repertoire in reelin mutant mice to explore the developmental precursors of the disorder. Our findings evidence a general delay in motor and vocal development in heterozygous (50% reduced reelin) and reeler (lacking reelin gene) mutant mice. As a whole, an increased number of calls characterized heterozygous pup's emission. Furthermore, the typical ontogenetic peak in the number of calls characterizing wild-type pups on postnatal day 4 appeared slightly delayed in heterozygous pups (to day 6) and was quite absent in reeler littermates, which exhibited a flat profile during development. We also detected a preferential use of a specific call category (two-components) by heterozygous and reeler mice at postnatal days 6 and 8 as compared to their wild-type littermates. With regard to the analysis of spontaneous movements, a differential profile emerged early in development among the three genotypes. While only slight coordination difficulties are exhibited by heterozygous pups, all indices of motor development appear delayed in reeler mice. Overall, our results evidence a genotype-dependent deviation in ultrasonic vocal repertoire and a general delay in motor development in reelin mutant pups.
Reelin 是一种大型分泌型细胞外基质糖蛋白，在早期神经发育中发挥重要作用。几项遗传研究发现 RELN 基因与自闭症风险增加之间存在关联，表明 reelin 缺乏可能是其发病机制中的一个脆弱因素。此外，在自闭症谱系障碍患者的几个大脑区域观察到 reelin 表达减少。由于许多报道记录了自闭症患者存在声音和运动神经功能障碍，并表明这些功能障碍先于综合征的发生，因此我们对 reelin 突变小鼠的新生声音和运动 repertoire 进行了精细的特征描述，以探索该疾病的发育前体。我们的研究结果表明，杂合子（reelin 减少 50%）和 reeler（缺乏 reelin 基因）突变小鼠的运动和声音发育普遍延迟。总的来说，杂合子幼鼠的叫声数量增加。此外，在第 4 天，野生型幼鼠叫声数量的典型发育高峰出现在第 6 天，而 reeler 同窝幼鼠则明显延迟，在发育过程中表现出平坦的曲线。我们还发现，与野生型同窝幼鼠相比，杂合子和 reeler 幼鼠在第 6 天和第 8 天更喜欢使用特定的叫声类别（两部分）。关于自发运动的分析，在三种基因型之间，早期发育出现了不同的模式。虽然杂合子幼鼠只表现出轻微的协调困难，但 reeler 幼鼠的所有运动发育指标都明显延迟。总的来说，我们的结果表明，reelin 突变幼鼠在超声发声谱中存在基因型依赖性偏差，运动发育普遍延迟。
