PLURIPOTENT STEM CELLS EDITION IN PLAKOPHILIN-2 GENE FOR ARRHYTHMOGENIC CARDIOMYOPATHY IN VITRO MODELING

GUADALUPE AMIN; SHEILA LUCIA CASTAÑEDA; ALAN MIQUEAS MÖBBS; MARIA AGUSTINA SCARAFÍA; CAROLINA COLLI; ANTONELLA LOMBARDI; ALEJANDRO DAMIÁN LA GRECA; CARLOS DANIEL LUZZANI; SANTIAGO GABRIEL MIRIUKA; LUCÍA NATALIA MORO

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

The arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disease characterized by the progressive replacement of contractile myocardium by fibro-fatty adipose tissue, generating ventricle arrhythmias and sudden death. The ACM has a genetic origin with mutations in desmosomal genes. Among these, one of the most commonly disrupted gene is Plakophilin-2 (PKP2), including non-sense mutations. Our aim was to evaluate PKP2 expression during cardiomyocyte differentiation, and to generate a PKP2 knockout (KO) iPSCs line by CRISPR/Cas9 in order to model the disease in-vitro. RNAseq data showed increased PKP2 expression during cardiomyocyte differentiation and this result was confirmed by Western blot (WB) analysis. We observed an increase of 8 times of PKP2 protein expression between day 0 and day 21 of differentiation (n= 2; p