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Abstract Details

The Role of the Signal Recognition Particle in Motor Neuron Development and Implications for SMA
Child Neurology and Developmental Neurology
Child Neurology and Developmental Neurology Posters (7:00 AM-5:00 PM)
063
To determine whether srp54 mutant zebrafish have similar motor axon defects to those in the SMA model.
The survival of motor neuron protein (SMN) is ubiquitously expressed and required in all cell types for viability. Motor neurons are especially sensitive to reduced SMN levels, made evident in the motor neuron disease spinal muscular atrophy (SMA). The observed neural specificity in SMA is not well understood. SMN functions in assembly of several ribonucleoprotein (RNP) complexes. One RNP with which SMN associates is the signal recognition particle (SRP), an RNP that regulates translation of secretory and transmembrane proteins. SRP assembly begins in the nucleus and is completed in the cytoplasm, where SMN assists in the addition of the final protein component, SRP54. To further investigate whether the SMN-SRP54 interaction is functionally relevant in SMA-susceptible motor neurons, we compared motor axon development in srp54 mutant zebrafish to that of the well-established zebrafish SMA model, where developing motor axons are truncated and aberrantly branched.
We obtained an srp54 nonsense allele that has a premature stop codon at amino acid 14 of 504 and is predicted to produce a severely truncated protein. Using immunohistochemistry, we characterized axonal outgrowth and neuromuscular junction development at different timepoints in srp54 mutant embryos and wild-type siblings.
Homozygous mutant srp54 zebrafish embryos initially appear morphologically normal; however, they exhibit reduced motility and marked motor axon defects that progressively worsen over developmental time. Compared to wild-type siblings, mutant motor axons are thinner and/or truncated with fewer projections and fewer neuromuscular junctions. The motor axon phenotype is reminiscent of that in the SMA model.
srp54 mutant zebrafish share common motor axon phenotypic features with the SMA model, providing additional support for the hypothesis that decreased SRP function may contribute to motor neuron susceptibility in SMA.
Authors/Disclosures
Nikaela Losievski
PRESENTER 		Miss Losievski has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Stephen J. Kolb, MD, PhD (The Ohio State University) Dr. Kolb has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AveXis. Dr. Kolb has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for CureSMA. The institution of Dr. Kolb has received research support from NIH. The institution of Dr. Kolb has received research support from AveXis. The institution of Dr. Kolb has received research support from NIH.