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. Overall design: 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.