In Skeletal Muscle Fibers, Protein Kinase Subunit CSNK2A1/CK2α Is Required for Proper Muscle Homeostasis and...

Area of Science:

• Muscle physiology and molecular biology
• Biochemistry of protein kinases
• Animal models for human disease

Background:

• The CSNK2 holoenzyme, comprising CSNK2A and CSNK2B subunits, regulates skeletal muscle homeostasis.
• Previous studies showed Csnk2a2 knockout mice had mild regenerative deficits and Csnk2b conditional knockout mice exhibited muscle weakness and metabolic dysfunction.

Purpose of the Study:

• To investigate the role of the CSNK2A1 subunit in skeletal muscle function by generating and characterizing skeletal muscle-specific conditional knockout mice.
• To compare the effects of CSNK2A1 ablation with known CSNK2B deficiencies in skeletal muscle.

Main Methods:

• Generation of skeletal muscle-specific conditional Csnk2a1 knockout mice using a Cre-lox system driven by a human skeletal actin promoter.
• Assessment of muscle strength (grip strength), neuromuscular transmission, and histological changes (central nuclei).
• Analysis of protein subunit levels, oxidative metabolism markers (cytochrome oxidase), mitochondrial enzyme activity, autophagy markers, and neuromuscular junction (NMJ) integrity.

Main Results:

• Conditional knockout of CSNK2A1 led to age-dependent reductions in grip strength and impaired neuromuscular transmission.
• CSNK2A1 ablation altered the expression of other CSNK2 subunits and increased central nuclei in muscle fibers, indicating regeneration.
• Impaired oxidative metabolism, stimulated autophagy, and fragmented NMJs with increased synaptic gene expression were observed.

Conclusions:

• Skeletal muscle-specific knockout of CSNK2A1 results in diverse functional and molecular impairments, including muscle weakness, altered metabolism, and NMJ defects.
• Both CSNK2A1 and CSNK2B deficiencies lead to distinct but significant disruptions in skeletal muscle biology.
• These findings underscore the critical role of CSNK2 subunits in maintaining skeletal muscle health and function.