PDF(Pubmed)
Abstract：
Recently, we described the alteration of six miRNAs in the serum of autistic children, their fathers, mothers, siblings, and in the sperm of autistic mouse models. Studies in model organisms suggest that noncoding RNAs participate in transcriptional modulation pathways. Using mice, approaches to alter the amount of RNA in fertilized eggs enable in vivo intervention at an early stage of development. Noncoding RNAs are very numerous in spermatozoa. Our study addresses a fundamental question: can the transfer of RNA content from sperm to eggs result in changes in phenotypic traits, such as autism? To explore this, we used sperm RNA from a normal father but with autistic children to create mouse models for autism. Here, we induced, in a single step by microinjecting sperm RNA into fertilized mouse eggs, a transcriptional alteration with the transformation in adults of glial cells into cells affected by astrogliosis and microgliosis developing deficiency disorders of the \'autism-like\' type in mice born following these manipulations. Human sperm RNA alters gene expression in mice, and validates the possibility of non-Mendelian inheritance in autism.
摘要：
最近,我们描述了自闭症儿童血清中六个miRNAs的变化，他们的父亲,母亲们,兄弟姐妹,在自闭症小鼠模型的精子中。模型生物的研究表明，非编码RNA参与转录调节途径。用老鼠，改变受精卵中RNA含量的方法可以在发育早期进行体内干预。精子中的非编码RNA非常多。我们的研究解决了一个基本问题：RNA含量从精子转移到卵子是否会导致表型性状的变化，比如自闭症？为了探索这个，我们使用正常父亲的精子RNA，但与自闭症儿童一起创建自闭症小鼠模型。这里,我们诱导，通过将精子RNA显微注射到受精卵中，在这些操作后出生的小鼠中，随着神经胶质细胞转化为受星形胶质细胞增生和小胶质细胞增生影响的细胞，发展为“自闭症样”型缺陷障碍的转录改变。人类精子RNA改变小鼠的基因表达，并验证了自闭症患者非孟德尔遗传的可能性。
