CRISPR/Cas9-mediated generation and analysis of N terminus polymorphic models of β₂AR in isogenic hPSC-derived cardiomyocytes.

ABSTRACT: During normal- and patho-physiological situations, the behavior of the beta2-adrenoreceptor (β₂AR) is influenced by polymorphic variants. The functional impact of such polymorphisms has been suggested from data derived from genetic association studies, in vitro experiments with primary cells, and transgenic overexpression models. However, heterogeneous genetic background and non-physiological transgene expression levels confound interpretation, leading to conflicting mechanistic conclusions. To overcome these limitations, we used CRISPR/Cas9 gene editing technology in human pluripotent stem cells (hPSCs) to create a unique suite of four isogenic homozygous variants at amino acid positions 16(G/R) and 27(G/Q), which reside in the N terminus of the β₂AR. By produ

SUBMITTER: Kondrashov A 

PROVIDER: S-EPMC7733025 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature