Mosaicism for the smooth muscle cell (SMC)-specific knock-in of the Acta2 R179C pathogenic variant: Implications for gene editing therapies

Pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections (TAD). De novo heterozygous ACTA2 variants disrupting arginine 179 cause Smooth Muscle Dysfunction Syndrome (SMDS), characterized by childhood onset TAD and cerebrovascular disease, with disruption of other smooth muscle cell (SMC)-dependent systems [1,2]. Because the human and mouse genes encode α-SMA with identical amino acid sequence, we sought to establish a SMDS mouse model to determine how this alteration causes a more severe phenotype than other ACTA2 mutations.

Source: Journal of Molecular and Cellular Cardiology - July 22, 2022 Category: Cytology Authors: Anita Kaw, Albert J. Pedroza, Abhijnan Chattopadhyay, Amelie Pinard, Dongchuan Guo, Kaveeta Kaw, Zhen Zhou, Rohan Shad, Michael P. Fischbein, Callie S. Kwartler, Dianna M. Milewicz Tags: Letter to the editor Source Type: research