Establishment and phenotypic analysis of a humanized mouse model for hypertrophic cardiomyopathy
MU Zhiqiang
HUANG Jiahui
LI Bowen
CHEN Kun
WU Yuanming
Abstract：Objective To simulate the phenotype of hypertrophic cardiomyopathy(HCM)in clinical patients by constructing a mouse model with a humanized FARS2 mutation.Methods The human FARS2 c.1244G＞T(p.R415L)gene was expressed in mice using gene-editing technology.After rearing to 4 months of age,the changes in cardiac tissue structure of mice were observed by HE,Masson's,and WGA staining,while cardiac function was evaluated by echocardiography.Finally,the changes in mitochondrial morphology was examined using transmission electron microscopy.Results Compared to wild-type controls,humanized mice showed no significant differences in cardiac HE,Masson's,and WGA staining.However,mice with the humanized point mutation exhibited a decline in cardiac function(P＜0.01)and partial structural alterations(P＜0.05).Additionally,transmission electron microscopy revealed vacuolar mitochondrial cristae structure,decreased cristae density,reduced mitochondrial number(P＜0.05)and significantly increased mitochondrial diameter(P＜0.01)in mice with the humanized point mutation.Conclusion The humanized FARS2 point mutant mouse model effectively simulates the development and progression of HCM in clinical patients,providing a mouse model for studying the mechanism and treatment of HCM.
Keywords：humanized micegene mutationFARS2hypertrophic cardiomyopathymitochondrial diseasesgene editingventricular functionechocardiography
Publication Date：2026-03-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：6( 421-426 )