Investigating the Role of PARylation in Regulating Skeletal Muscle Mass and Function in Healthy Mature Mice

Abstract

Adenosine diphosphate (ADP) ribosylation is a post-translational modification dependent on the transfer of ADPr units from nicotinamide adenine dinucleotide (NAD+) on to a plethora of biomolecules (i.e., proteins, DNA, RNA, etc.) in response to physiological stressors (i.e., nutrient deprivation, oxidative stress, DNA strand breaks). Poly-ADP-ribosylation (PARylation) is primarily mediated by the family of poly(ADP-ribose) polymerases (PARPs) and enzymatically degraded (dePARylation) by hydrolases such as poly(ADP-ribose) glycohydrolase (PARG). This thesis characterizes the role of poly(ADP-ribose) polymerase 1 (PARP1) and PARG in the skeletal muscle of healthy mature mice under normal physiological conditions. Specifically, we validate the deletion of Parp1 and Parg in inducible skeletal muscle-specific KO mouse models followed by performing general phenotyping of both male and female mice. The thesis concludes that under normal physiological conditions the activity of Parp1 or Parg in (de)PARylation is dispensable for maintaining skeletal muscle mass, function, and homeostasis in healthy mature mice.