Cardiac Myocyte-Specific Deletion of Ataxia Telangiectasia-Mutated Kinase (ATM) Induces Left Ventricular Dilation and Systolic Dysfunction
Abstract
Background: Mutations in ATM gene cause an autosomal disease known as Ataxia-telangiectasia (A-T). Whole-body ATM knockout (KO) mice die ~2 to 4 months of age. At ~2 months of age, these mice exhibit reduced left ventricular (LV) dilation with no change in percent fractional shortening (%FS) and ejection fraction (%EF) versus wild type. This study investigated if cardiac myocyte-specific deletion of ATM induces LV dilation and cardiac dysfunction. Methods: Cardiac myocyte-specific ATM KO mice (fl/fl/cre) and their controls (flox/flox; fl/fl) were generated by cross breeding of ATM flox/flox and αMyHC-cre mice. Cardiac structural and functional parameters were measured using echocardiography. M-mode images were used to measure %FS, %EF, LV end-systolic (ESD) and end-diastolic (EDD) diameters, end-diastolic (EDV) and end-systolic (ESV) volumes in mice aged 4 and 8 months. Results: Cardiac myocyte-specific deletion of ATM significantly increased EDD in fl/fl/cre versus fl/fl mice aged 4 months. However, a significant decrease in %FS and %EF was observed in fl/fl/cre versus fl/fl group in mice aged 8 months. Conversely, fl/fl/cre exhibited a significant increase in ESD, EDD, ESV, and EDV versus fl/fl mice. Conclusion: Thus, cardiac myocyte-specific deletion of ATM induces LV dilation in mice aged 4 & 8 months and systolic dysfunction in mice aged 8 months. This research was supported by the Department of Biomedical Health Sciences and the Department of Biomedical Sciences.
Start Time
16-4-2025 1:30 PM
End Time
16-4-2025 4:00 PM
Presentation Type
Poster
Presentation Category
Science, Technology and Engineering
Student Type
Undergraduate Student
Faculty Mentor
Suman Dalal
Faculty Department
Biomedical Health Sciences
Cardiac Myocyte-Specific Deletion of Ataxia Telangiectasia-Mutated Kinase (ATM) Induces Left Ventricular Dilation and Systolic Dysfunction
Background: Mutations in ATM gene cause an autosomal disease known as Ataxia-telangiectasia (A-T). Whole-body ATM knockout (KO) mice die ~2 to 4 months of age. At ~2 months of age, these mice exhibit reduced left ventricular (LV) dilation with no change in percent fractional shortening (%FS) and ejection fraction (%EF) versus wild type. This study investigated if cardiac myocyte-specific deletion of ATM induces LV dilation and cardiac dysfunction. Methods: Cardiac myocyte-specific ATM KO mice (fl/fl/cre) and their controls (flox/flox; fl/fl) were generated by cross breeding of ATM flox/flox and αMyHC-cre mice. Cardiac structural and functional parameters were measured using echocardiography. M-mode images were used to measure %FS, %EF, LV end-systolic (ESD) and end-diastolic (EDD) diameters, end-diastolic (EDV) and end-systolic (ESV) volumes in mice aged 4 and 8 months. Results: Cardiac myocyte-specific deletion of ATM significantly increased EDD in fl/fl/cre versus fl/fl mice aged 4 months. However, a significant decrease in %FS and %EF was observed in fl/fl/cre versus fl/fl group in mice aged 8 months. Conversely, fl/fl/cre exhibited a significant increase in ESD, EDD, ESV, and EDV versus fl/fl mice. Conclusion: Thus, cardiac myocyte-specific deletion of ATM induces LV dilation in mice aged 4 & 8 months and systolic dysfunction in mice aged 8 months. This research was supported by the Department of Biomedical Health Sciences and the Department of Biomedical Sciences.