Deficiency in Kelch protein Klhl31 causes congenital myopathy in mice

摘要: Maintenance of muscle structure and function depends on the precise organization contractile proteins into sarcomeres coupling apparatus to sarcoplasmic reticulum (SR), which serves as reservoir for calcium required contraction. Several members Kelch superfamily proteins, modulate protein stability substrate-specific adaptors ubiquitination, have been implicated in sarcomere formation. The Klhl31 is expressed a muscle-specific manner under control transcription factor MEF2. To explore its functions vivo, we created mouse model loss using CRISPR-Cas9 system. Mice lacking exhibited stunted postnatal skeletal growth, centronuclear myopathy, central cores, Z-disc streaming, SR dilation. We used proteomics identify several candidate substrates, including Filamin-C (FlnC). In Klhl31-knockout mice, FlnC levels were highly upregulated with no change transcription, further demonstrated that targets ubiquitination degradation. These findings highlight role maintenance provide insight mechanisms underlying congenital myopathies.