Genetic Models of Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Dis Model Mech. 2010 May-Jun;3(5-6):366-76. doi: 10.1242/dmm.003442. Epub 2010 Jan 18.
Neuroligins are postsynaptic cell adhesion proteins that bind specifically to presynaptic membrane proteins called neurexins. Mutations in human neuroligin genes are associated with autism spectrum disorders in some families. The nematode Caenorhabditis elegans has a single neuroligin gene (nlg-1), and approximately a sixth of C. elegans neurons, including some sensory neurons, interneurons and a subset of cholinergic motor neurons, express a neuroligin transcriptional reporter. Neuroligin-deficient mutants of C. elegans are viable, and they do not appear deficient in any major motor functions. However, neuroligin mutants are defective in a subset of sensory behaviors and sensory processing, and are hypersensitive to oxidative stress and mercury compounds; the behavioral deficits are strikingly similar to traits frequently associated with autism spectrum disorders. Our results suggest a possible link between genetic defects in synapse formation or function, and sensitivity to environmental factors in the development of autism spectrum disorders.
神经连接蛋白是突触后细胞粘附蛋白，特异性地与突触前膜蛋白神经连接蛋白结合。人类神经连接蛋白基因的突变与某些家族的自闭症谱系障碍有关。线虫秀丽隐杆线虫只有一个神经连接蛋白基因（nlg-1），大约六分之一的秀丽隐杆线虫神经元，包括一些感觉神经元、中间神经元和一部分胆碱能运动神经元，表达神经连接蛋白转录报告基因。秀丽隐杆线虫的神经连接蛋白缺陷突变体是可行的，它们似乎没有任何主要运动功能的缺陷。然而，神经连接蛋白突变体在一部分感觉行为和感觉处理方面存在缺陷，并且对氧化应激和汞化合物敏感；这些行为缺陷与自闭症谱系障碍经常相关的特征非常相似。我们的结果表明，突触形成或功能的遗传缺陷与自闭症谱系障碍发展过程中对环境因素的敏感性之间可能存在联系。
