Consequences of IRF2BP2 Loss of Function in Mouse Development and Skeletal Muscle Regeneration

Abstract

IRF2BP2 is a corepressor of IRF2, a transcription factor involved in the immune response. IRF2BP2 is also a coactivator of the VGLL4/TEAD4 complex in muscle. Given its functional duality, we asked how IRF2BP2 deletion would affect mouse development and adult muscle regeneration. Most Irf2bp2-/- mice die prior to birth, those that survive develop lymphoma in adulthood. Microarray profiling of Irf2bp2 knockout liver, heart, and skeletal muscle revealed a shared program of upregulated genes involved in inflammation and immunity. The function of IRF2BP2 in adult skeletal muscle recovery from cardiotoxin-induced injury was evaluated. Compared to WT mice, mice with macrophage-specific ablation of IRF2BP2 (Irf2bp2flox/LysMCre) or muscle-specific ablation of Irf2bp2 (Irf2bp2flox/MckCre) mice showed increased inflammation and impaired muscle regeneration. Global deletion of Irf2bp2 in mice results predominantly in embryonic death or lymphoma in adults. Irf2bp2 suppresses genes that mediate inflammation in mouse liver, heart, and in skeletal muscle, where IRF2BP2 promotes regeneration.