Loss of AnkB upregulates stress-related pathways in skeletal muscle

Human mutations in the ANK2 gene, which encodes ankyrin B (AnkB), lead to age- and diet-induced metabolic syndrome in mice. To investigate the contribution of skeletal muscle (SKM) AnkB to systemic energy balance and metabolic homeostasis, we developed skeletal muscle (SKM)-specific AnkB knockout (KO) (Ank2f/f; HSA-Cre+) mice. Physiological,cellular, biochemical and transcriptional characterization of these mice uncovered a muscle-autonomous role of AnkB in maintaning mitochondria health and muscle energetic homeostasis via the regulation of mitochondrial dynamics and sarcoplasmic reticulum (SR) organization. We isolated total RNA from gastrocnemius muscle of control (WT) and Ank2 knock-out (KO) adult mice (4-month-old, n=6 mice/group) selectively lacking AnkB (Ank2) in skeletal muscle. We evaluated differential gene expression via paired-end RNA-seq analysis.