Identification of Ankrd2, a novel skeletal muscle gene coding for a stretch-responsive ankyrin-repeat protein

Abstract

Mechanically induced hypertrophy of skeletal muscles involves shifts in gene expression leading to increases in the synthesis of specific proteins. Full characterization of the regulation of muscle hypertrophy is a prerequisite for the development of novel therapies aimed at treating muscle wasting (atrophy) in human aging and disease. Using suppression subtractive hybridization, cDNAs corresponding to mRNAs that increase in relative abundance in response to mechanical stretch of mouse skeletal muscles in vivo were identified. A novel 1100-bp transcript was detected exclusively in skeletal muscle. This exhibited a fourfold increase in expression after 7 days of stretch. The transcript had an open reading frame of 328 amino acids encoding an ATP/GTP binding domain, a nuclear localization signal, two PEST protein-destabilization motifs, and a 132-amino-acid ankyrin-repeat region. We have named this gene ankyrin-repeat domain 2 (stretch-responsive muscle) (Ankrd2). We hypothesize that Ankrd2 plays an important role in skeletal muscle hypertrophy.