Abstract 14488: Male Predominant Cardiac Phenotype in Cardiac-Specific Gpd1-l Knockout Mice

• DOI: 10.1161/circ.148.suppl_1.14488
• Publication Date: 2023-12-19T07:59:21Z
• Authors: Haider Mehdi; Alexander Greiner; Jason Dierdorff; Jin-Young Yoon; Kyle Current; William J Kutschke; Diana Colgan; Barry London
• Keywords: Knockout mouse

Introduction: We reported that a mutation in Glycerol-3-Phosphdate Dehydrogenase-1 Like (GPD1L-A280V) is linked to Brugada Syndrome (BrS). This increases acetylation and reduces surface expression of Nav1.5, inward Na+ current (INa) HEK293 cells rat neonatal cardiac myocytes. Global homozygous knockout Gpd1-l mice (Gpd1l-/-) was usually lethal, though we noted increased Nav1.5 acetylation, decreased INa, pharmacologically inducible arrhythmias Gpd1l+/- heterozygotes. Cardiac-specific deletion Gpd1l (cGpd1l-/-) led ventricular arrhythmias, contractile dysfunction, BrS-like ECG phenotype males. Here, extend our study female cGpd1l-/- mice. Methods: cGpd1l -/- were generated by crossing floxed (Gpd1l fl/fl ) with αMHC-Cre expressing ECGs echocardiograms (echos) recorded at 6 9 months age littermate controls. Results: At age, male compared Gpd1lfl/fl controls had end diastolic systolic volumes (EDV, 108±67 vs 27±3 μL, p=0.02; ESV; 80±66 6±2 μL; p=0.03), markedly reduced ejection fractions (EF, 33±18% vs. 77±7%, p=0.001). Female mice, on the other hand, no changes EDV, ESV, or EF (Figure A). The echo minimal months. recordings ~9-month-old showed prolonged PR interval (52±1.1 40±2.7 ms; p=0.05) QRS duration (17.8±1.5 15.2±1.1 p=0.01) change heart rate B). parameters also unchanged Conclusions: disruption causes conduction abnormalities but not Further investigation into mechanisms underlying sex-dependent Gpd1l-/-mice whether this impacts predominance BrS humans warranted.