Virginia Via Research Day Book 2026

Undergraduate Student Research Biomedical

06 DEVELOPMENT OF DILATED CARDIOMYOPAHTY AND HEART FAILURE IN MEIS-1 KNOCKOUT MICE

Claudia Ramos-Lopez, Alyssa Morrison, Junting Zhou, Austin Mason, Claire Cho, Alina Xie, Allyson Meador, Reece Girdharry, Ian Jeong, Sam Castellani, Braxton McDaniel, and Dr. Jia-Qiang He Corresponding author: claudiar24@vt.edu

Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia

Dilated cardiomyopathy (DCM) is a major cause of heart failure worldwide, affecting 36 out of 100,000 patients. It is characterized by heart enlargement due to the left ventricular dilation, which thins and stretches the ventricular walls and makes the heart unable to pump blood efficiently. Although multiple genetic and molecular contributors have been identified, the precise mechanisms underlying disease onset remain incompletely understood. Myeloid ecotropic viral integration site 1 (Meis1) is a transcription factor critical for embryonic organ development, limb formation, and vascular patterning. Beyond its developmental roles, Meis1 is also found in regulating cell proliferation and differentiation, contributing to nervous system function, as well as being involved in cancer progression, such as leukemia. Recently, studies indicate Meis1 plays a key role in cardiac development and regeneration, probably through modulating mitochondrial function and cardiomyocyte cell cycle after birth. However, how Meis1 regulates

the adult’s heart health is largely unclear. In this study, we conducted a series of experiments to explore the structure and functional changes of the mouse hearts from wild-type (WT) and cardiac specific Meis1 knockout (Meis1-KO) mice. Briefly, genotyping was performed on all mice to verify their genetic status, ensuring accurate identification of WT and Meis1-KO. Echocardiography was performed to assess cardiac structure and function remodeling. Electrocardiography (ECG) was used to evaluate cardiac electrical activity. The hearts were perfused and enzymatically digested to obtain single isolated cardiomyocytes to measure cell contraction. Meis1-KO and WT mice were examined across multiple ages ranging from early adulthood (~ 1 .5 months old), intermediate stage (~2.5 months old), to advanced stages (~5.5 months old) of both female and male groups. Echocardiography revealed significantly enlarged size of the left ventricular chamber, reduced fractional shortening (FS%) and ejection fraction (EF%), which is consistent with ventricular dilation

and systolic decline in Meis1-KO mice. ECG traces demonstrated decreased amplitudes of various waves and arrhythmic events in Meis1-KO mice, compared to WT, suggesting the damaged cellular and molecular comportments associated with the action potentials in Meis1-KO mice. Furthermore, in vitro contraction analysis of isolated single cardiomyocyte confirmed reduced contractility at the cellular level. Notably, these structural and functional deficits became increasingly apparent as the knockout mice aged, implying a gradual deterioration of cardiac structure and function over time. Future work will include cardiac histological analysis, gene and protein expression analysis, which will provide a more detailed mechanistic understanding of Meis1-KO-indcued DCM and heart failure.

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