Value Proposition
· Drug-sensitive TrkB receptors: F616A mutation creates unique binding pocket allowing selective inhibition by specific small molecules
· BDNF pathway research tool: Enables targeted study of the most clinically relevant neurotrophin signaling pathway in neuropsychiatric disorders
· Selective inhibition capability: Mutant TrkB receptors can be pharmacologically blocked without affecting other kinases or wild-type TrkB
· In vivo research applications: Allows TrkB inhibition studies in living animals across different developmental stages and disease models
Unmet Need
Neuroscience researchers studying BDNF-TrkB signaling lack adequate tools to selectively inhibit TrkB activity in living animal models. Traditional genetic knockout approaches permanently eliminate TrkB function, preventing researchers from studying the specific effects of TrkB inhibition in adult animals or disease contexts. Current pharmacological inhibitors lack the specificity needed to isolate TrkB effects from other kinase targets, limiting their utility in mechanistic studies.
Technology Description
Researchers at Johns Hopkins developed genetically modified mice carrying an F616A point mutation in the TrkB neurotrophin receptor kinase domain. This mutation alters the ATP-binding pocket of TrkB, making it uniquely susceptible to inhibition by engineered small molecule compounds that do not affect wild-type TrkB or other kinases. The mice provide a research platform for studying BDNF-TrkB pathway function through selective pharmacological intervention.
Stage of Development
These mouse strains have been validated.
Data Availability
· n/a
Publication
Chen X, Ye H, Kuruvilla R, Ramanan N, Scangos KW, Zhang C, Johnson NM, England PM, Shokat KM, Ginty DD. A chemical-genetic approach to studying neurotrophin signaling. Neuron. 2005 Apr 7;46(1):13-21. doi: 10.1016/j.neuron.2005.03.009. PMID: 15820690.
