Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.12.149104v1?rss=1 Authors: You, H., Mizui, T., Kiyosue, K., Takao, K., Miyakawa, T., Kato, K., Otsuka, M., Bai, T., Xia, K., Lu, B., Kojima, M. Abstract: Autism spectrum disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is oppositely regulated by brain-derived neurotrophic factor (BDNF): the precursor proBDNF inhibits while mature BDNF (mBDNF) potentiates synapses. Here we generated a knock-in mouse line (BDNFmet/leu) in which the conversion of proBDNF to mBDNF is inhibited. Similar to other ASD mouse models, the BDNFmet/leu mice showed decreased brain volumes, reduced dendritic arborization, altered spines, and impaired synaptic transmission and plasticity. They also exhibited ASD-like phenotypes, including stereotypical behaviors, deficits in social interaction, hyperactivity, and elevated stress response. Interestingly, the plasma level of proBDNF, but not mBDNF, was significantly elevated in ASD patients. These results suggest that proBDNF level, but not Bdnf gene, is associated with autism-spectrum behaviors, and identify a potential blood marker and therapeutic target for ASD. Copy rights belong to original authors. Visit the link for more info