Value Proposition
· Visualization tool: FLAG-tagged TrkA knock-in mouse that allows direct tracking of endogenous TrkA receptor trafficking and signaling in living neurons
· Physiologically relevant: Unlike overexpression systems, this model maintains normal TrkA expression levels and regulation from the endogenous locus
· Versatile research applications: Enables studies of neurotrophin signaling, synaptic development, pain pathways, and neurodevelopmental disorders
· Technical advantages: FLAG epitope allows for easy immunodetection, purification, and live imaging without disrupting normal TrkA function
· Validated functionality: Homozygous mice are viable and fertile, indicating the FLAG tag doesn't interfere with essential TrkA functions
· Broad research utility: Applicable to studies of both peripheral and central nervous system development and disease
Unmet Need
Understanding neurotrophin receptor trafficking and signaling dynamics is critical for advancing treatments for neurological disorders, pain conditions, and neurodevelopmental diseases. Current methods for studying TrkA receptor biology rely primarily on overexpression systems, antibodies, or biochemical approaches that don't allow real-time visualization of receptor dynamics in living systems. These existing approaches have significant limitations including altered expression levels, poor antibody specificity, inability to track receptors in real-time, and difficulty distinguishing between different pools of receptors within neurons. Therefore, there is a strong need for a method to precisely track endogenous TrkA receptors to advance our understanding of neurotrophin signaling mechanisms.
Technology Description
Researchers at Johns Hopkins have developed a novel FLAG-tagged TrkA knock-in mouse model that allows for visualizing endogenous neurotrophin receptor trafficking and signaling in living neurons. This mouse strain expresses a FLAG epitope-tagged version of the TrkA neurotrophin receptor from its native chromosomal location, allowing researchers to visualize and track endogenous TrkA receptors without altering their normal expression patterns or cellular functions. The technology enables real-time monitoring of TrkA receptor trafficking, signaling endosome formation, and synaptic targeting in both peripheral and central nervous system neurons.
Stage of Development
· This strain is available on Jax Lab’s repository:
o JAX # 013720 B6.129S6(Cg)-Ntrk1tm2Ddg/J
Data Availability
· n/a
Publication
Mandai K; Guo T; St Hillaire C; Meabon JS; Kanning KC; Bothwell M; Ginty DD. 2009. LIG family receptor tyrosine kinase-associated proteins modulate growth factor signals during neural development. Neuron 63(5):614-27. [PubMed: 19755105]
Sharma N; Deppmann CD; Harrington AW; St. Hillaire C; Chen ZY, Lee FS; Ginty DD. 2010 Long-distance control of synapse assembly by target-derived NGF. Neuron 67(3): 422-34. [PubMed: 20696380]
