Knock-in Kcnh2 rabbit model of long QT syndrome type-2, epilepsy, and sudden death.

ABSTRACT:

Background

Long QT Syndrome Type-2 (LQT2) is due to loss-of-function KCNH2 variants. KCNH2 encodes K_v11.1 that forms a delayed-rectifier potassium channel in the brain and heart. LQT2 is associated with arrhythmias, seizures, sudden cardiac death, and sudden unexpected death in epilepsy (SUDEP). The goal of the study is to develop a translational model that reproduces the neuro-cardiac electrical abnormalities and sudden death seen in people with LQT2.

Methods

We generated the first knock-in rabbit model of LQT2 (Kcnh2^(+/7bp-del)), due to a 7 base-pair (7bp) deletion in the pore domain of the endogenous rabbit Kcnh2 gene.

Results

Mutant Kcnh2 is expressed in the heart and brain and constitutes 11% of total Kcnh2 in Kcnh2^(+/7bp-del) rab

SUBMITTER: Singh V 

PROVIDER: S-EPMC12001650 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature