Increased Insulin Action, Glucose Metabolism and Muscle Function in Supervillin-knockout and Supervillin-mutant Mice

In skeletal muscle, Svil-Mut mice express the Svil-encoded N-terminus fused to the bgal-neo gene trap tag and lack the highly conserved archvillin C-terminus; Svil-KO mice lack expression of all known Svil-encoded proteins; and Svil-loxP mice contain loxP sites for tissue-specific disruption of protein expression. Older Svil-KO male mice showed decreased levels of markers for type 1, 2a and 2b muscle fibers.

Male mice showed elevated pERK/ERK signaling during lengthening contractions, consistent with low-level muscle damage such as that seen in myofibrillar myopathy-10 in humans lacking SVIL proteins. Female mice lacking full-length Svil-encoded proteins, including supervillin and archvillin, exhibited reduced body weights and reduced fat mass. Females in both strains exhibited improved glucose tolerance and lower insulin levels following intraperitoneal glucose injections.