A multifaceted approach for analyzing complex phenotypic data in rodent models of autism

Abstract

AutDB features a modular framework that aims at collating multifactorial risk factors associated with autism spectrum disorder (ASD). The animal model (AM) module of AutDB was first developed for mouse models of genes and CNVs associated with ASD (Kumar et al., 2011). Subsequently, environmentally induced rodent models were introduced to capture the full spectrum of risk-factors associated with ASD, along with idiopathic models represented by inbred strains. Using the data systematically annotated in AutDB, we depict the intricate trends in the research findings based on rodent models of ASD. We identify the top 30 most frequently studied phenotypes extracted from 911 genetic, 269 induced and 17 inbred rodent models of ASD extracted from 787 publications. As expected, many of these include animal model equivalents of the core phenotypes associated with ASD, as well as several comorbid features of ASD including anxiety, seizures and motor-control deficits. Uniquely, AutDB curates rescue models where various treatment strategies were used in rodent ASD models to alleviate ASDrelevant phenotypes. We further examine ASD models based on 52 genes and 2 CNV loci to identify 24 pharmaceutical agents that were used in 2 or more paradigms for testing their efficacy. As a case study, we analyze various Shank3 mouse models providing a highresolution view of the in vivo role of this high-confidence ASD gene. Together, this resource provides a snapshot of genetic and induced models of ASD within a shared annotation platform to examine the complex meshing of diverse ASD-associated risk-factors.