Generation of a Mouse Model with Tissue-Specific Deletion of the Cap Gene – CAP2mini

The proper functioning of the neuromuscular system is essential for both breathing and movement. Signals from the brain are transmitted to motor neurons located in the spinal cord and reach neuromuscular junctions (NMJs) via long projections known as axons. NMJs allow the transmission of signals that trigger muscle contraction from axons to skeletal muscle fibers. The actin cytoskeleton plays a crucial role in organizing the muscle contraction machinery, structuring NMJs, and ensuring appropriate development of motor neuron axons. Cap2 is a protein that regulates the actin cytoskeleton by controlling the disassembly of actin filaments as well as the polymerization of actin within fiber structures (Ono et al., J Cell Sci 2013). The role of Cap2 in the neuromuscular system remains poorly understood.

Findings obtained by our team to date indicate that mice with Cap2 deletion exhibit a range of abnormalities in both the presynaptic and postsynaptic components of the neuromuscular junction. The goal of the Miniatura project is to generate mice with tissue-specific deletion of Cap2 in (a) skeletal muscles, (b) motor neurons, and (c) neurons of the central nervous system, and to collect preliminary data demonstrating which cell type may be responsible for each phenotype. The analyses will focus particularly on synapse size and fragmentation within the neuromuscular junction, the organization of motor neurons—including potential neurodegenerative changes such as axonal swellings—and the number of neurons innervating individual synapses. Comparing results from mice with Cap2 deletion in skeletal muscles, motor neurons, and the brain will provide preliminary insights suggesting how each cell type contributes to specific phenotypes.