Characterization of ACSS2 deficiency in skeletal muscle

Topic:

Translational Research

Poster Number: T379

Author(s):

Gloriana Campos, BS, University of Minnesota- Twin Cities, Natalya Wells, BS, Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Mekala Gunasekaran, PhD, Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Khanhlinh Lambuu, BS, Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Audrey Daugherty, BS, Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Peter Kang, MD, Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School

Acetyl-CoA synthetase 2 (ACSS2) is a key enzyme that converts acetate to acetyl-CoA, which is a major metabolite in carbohydrate and fat metabolism. Acss2 promotes systemic storage of lipids in the mouse liver, linking Acss2 to fatty liver disease and obesity. A prior study suggests that fasted Acss2 knockout mice had locomotor impairments, indicating that ACSS2 deficiency might have an impact on skeletal muscle function. This project focuses on characterizing Acss2 deficiency in mouse skeletal muscle. Crossing of heterozygous Acss2+/- mice yielded homozygous Acss2-/- mice less frequently than expected, suggesting that some homozygotes experience embryonic lethality. The homozygous mice displayed decreased body weight and length in both sexes. Primary mouse myoblasts isolated from neonatal homozygous mice showed impaired differentiation. There was a significant decrease in muscle weights, along with varied cross-sectional area of the muscle fibers in homozygous mice. Histological examination of skeletal muscle samples from Acss2-/- mice showed decreased proportions of type I fibers compared to wild type mice. The results from this study will provide more information on the effects of ACSS2 on skeletal muscle development and health.