Proximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions

Authors: Yudong Gao, Daichi Shonai, Matthew Trn, Jieqing Zhao, Erik J. Soderblom, S. Alexandra Garcia-Moreno, Charles A. Gersbach, William C. Wetsel, Geraldine Dawson, Dmitry Velmeshev, Yong-hui Jiang, Laura G. Sloofman, Joseph D. Buxbaum and Scott H. Soderling

Nature Communications, 09 August 2024

Scientists use Maestro MEA to explore the underlying mechanisms of autism spectrum disorder in vitro. 

Despite robust research, the underlying mechanisms of autism spectrum disorder are not fully understood. In this study, scientists develop a genome-editing approach to analyze the spatial proteomes of 14 autism risk genes in a mouse model to identify interactions that may help prioritize genetic risk factors. To assess a potential interaction between Syngap1 and Anks1b, proteins with overlapping proteomes and pathway enrichment suggesting regulation of glutamatergic activity in autism, the researchers used Axion’s noninvasive Maestro multielectrode array (MEA). Analysis revealed that the loss of Syngap1 function resulted in accelerated network activity during the synaptogenic development period. This effect was exacerbated by loss of both Syngap1 and Anks1b function, suggesting a functional interaction between them hypothesized to be due to glutamate receptor development identified in the overlapping proteomes. Overall, according to the authors, “the findings reveal enriched native proteome networks related to autism, suggesting new avenues for understanding and potentially manipulating the cellular mechanisms involved in the disorder.”