Cellular Models and High-Throughput Screening for Genetic Causality of Intellectual Disability.

Cellular Models and High-Throughput Screening for Genetic Causality of Intellectual Disability.
Trends Mol Med. 2021 Jan 02;:
Authors: Fell CW, Nagy V
Abstract
Intellectual disabilities (ID) are a type of neurodevelopmental disorder (NDD). They can have a genetic cause, including an emerging class of ID centring around Rho GTPases, such as Ras-related C3 botulinum toxin substrate 1 (RAC1). Guidelines for establishing genetic causality include the use of cellular models, which often have morphological aberrations, a long-standing hallmark of ID. Disease cellular models can facilitate high-throughput screening (HTS) of chemical or genetic perturbations, which can provide translatable biological insight. Here, we discuss a class of IDs centring around RAC1. We review novel and established cellular models of ID, including mouse and human primary cells and reprogrammed or induced neurons. Finally, we review progress and remaining challenges in the adoption of HTS methodologies by the community studying neurological disorders.
PMID: 33397633 [PubMed - as supplied by publisher]

Source: Trends in Molecular Medicine - January 2, 2021 Category: Molecular Biology Authors: Fell CW, Nagy V Tags: Trends Mol Med Source Type: research