PTPRD and PTPRS in Adult Mouse Neuromuscular Synapse Maintenance

Authors:

Daniel J. Lian, Dan Hathaway, Zhigang He

Date Created:

2025-01-01

Course Title:

Professor:

Not specified

About Paper:

In many neuromuscular disorders, such as amyotrophic lateral high AAV transduction efficiency via costaining with the motor sclerosis or myasthenia gravis, the motor axon retracts from neuron marker ChAT. Subsequently, we progressed to the second the neuromuscular junction, disrupting the brain’s ability objective, which is to implement this optimized model to knockout to control the muscle. Identifying pathways that promote Ptprs/Ptprd andevaluatetheimpactonsynapsemaintenanceinthe presynaptic differentiation are a promising strategy for promoting diaphragm. We generated AAV9/retro-virus expressing different reinnervation. Past work has shown that the postsynaptic protein multiplexed gRNA cassettes targeting Ptprs, Ptprd, or both genes. LRP4 binds to presynaptic receptors PTPRD and PTPRS, to Using our approach from our first objective, we introduced these activate synaptic differentiation during mouse development. gRNA expressing viruses into ChAT-Cre; LSL-Cas9-EGFP mice. Our project focuses on determining if Ptprs/Ptprd expression After isolating the diaphragms of mice one-month post injection, is necessary for the maintenance of the neuromuscular synapse we employed antibody staining of beta-3 tubulin and synapsin to in adult mice, and overall if reactivation of this pathway has evaluate the morphology of the axons and presynaptic terminals. therapeutic potential in neuromuscular disorders. The first Confocal imaging and analysis of the whole-mounted diaphragms objective was to establish an AAV-based system for efficiently are currently underway. Further efforts will concentrate on transducing and labelling spinal motor neurons. We generated verifying successful Ptprs/Ptprd knockout using immunostaining AAV9/retro virus expressing the reporter gene H2B-GFP and and quantifying the morphological changes after knockout as well performed subcutaneous injection of P0 mice. We then verified as any changes to motor performance.

Abstract:

In many neuromuscular disorders, such as amyotrophic lateral high AAV transduction efficiency via costaining with the motor sclerosis or myasthenia gravis, the motor axon retracts from neuron marker ChAT. Subsequently, we progressed to the second the neuromuscular junction, disrupting the brain’s ability objective, which is to implement this optimized model to knockout to control the muscle. Identifying pathways that promote Ptprs/Ptprd andevaluatetheimpactonsynapsemaintenanceinthe presynaptic differentiation are a promising strategy for promoting diaphragm. We generated AAV9/retro-virus expressing different reinnervation. Past work has shown that the postsynaptic protein multiplexed gRNA cassettes targeting Ptprs, Ptprd, or both genes. LRP4 binds to presynaptic receptors PTPRD and PTPRS, to Using our approach from our first objective, we introduced these activate synaptic differentiation during mouse development. gRNA expressing viruses into ChAT-Cre; LSL-Cas9-EGFP mice. Our project focuses on determining if Ptprs/Ptprd expression After isolating the diaphragms of mice one-month post injection, is necessary for the maintenance of the neuromuscular synapse we employed antibody staining of beta-3 tubulin and synapsin to in adult mice, and overall if reactivation of this pathway has evaluate the morphology of the axons and presynaptic terminals. therapeutic potential in neuromuscular disorders. The first Confocal imaging and analysis of the whole-mounted diaphragms objective was to establish an AAV-based system for efficiently are currently underway. Further efforts will concentrate on transducing and labelling spinal motor neurons. We generated verifying successful Ptprs/Ptprd knockout using immunostaining AAV9/retro virus expressing the reporter gene H2B-GFP and and quantifying the morphological changes after knockout as well performed subcutaneous injection of P0 mice. We then verified as any changes to motor performance.

Source:

Harvard / Harvard College | Kirkland House | Electrical Engineering | 2027 / 2025

Topics:

ptprd, ptpr, neuromuscular, motor, mice, objective, knockout, presynaptic, diaphragm, expressing, adult, mouse

Co-authors:

@danieljlian317 , @danhathaway318 , @zhiganghe297