Value Proposition
· Enhanced labeling efficiency: The TH-2A-CreER mouse line achieves higher labeling efficiency compared to existing mouse lines through the 2A peptide system that ensures elevated CreER expression levels
· Multi-population targeting: Enables labeling and functional manipulation of TH-expressing neuronal populations including sympathetic neurons, C-LTMRs (somatosensory neurons), and nigrostriatal neurons
· Temporal control: Provides tamoxifen-inducible gene expression control, allowing researchers to activate reporter genes at specific developmental stages or experimental timepoints
· System compatibility: Compatible with Cre-dependent reporter mice and Cre-lox system tools for diverse experimental applications
· Consistent performance: Demonstrates excision patterns matching endogenous TH expression in sympathetic ganglia, dorsal root ganglia, and retina
Unmet Need
Catecholaminergic neurons synthesize neurotransmitters including dopamine, norepinephrine, and epinephrine through a pathway initiated by tyrosine hydroxylase (TH), the rate-limiting enzyme that converts L-tyrosine to L-DOPA. Current methods for studying TH-expressing neurons rely on traditional Cre-expressing mouse lines or viral approaches, which exhibit low labeling efficiency, variable expression levels, and limited temporal control. These limitations restrict researchers' ability to conduct functional studies of TH-expressing neuronal circuits and their roles in behavior and disease. Therefore, there is a need for improved genetic tools with enhanced labeling efficiency and temporal control to study TH-expressing neurons.
Technology Description
Researchers at Johns Hopkins have developed a mouse genetic tool that addresses the need for efficient labeling and manipulation of tyrosine hydroxylase-expressing neurons. The TH-2A-CreER mouse line combines a 2A peptide system with tamoxifen-inducible Cre recombinase technology to achieve enhanced labeling efficiency of TH-expressing neuronal populations.
Stage of Development
· This mutant mouse strain is available on Jax Lab’s repository:
o Jax# 025614 STOCK Thtm1.1(cre/ERT2)Ddg/J
Data Availability
· n/a
Publication
Abraira VE, Kuehn ED, Chirila AM, Springel MW, Toliver AA, Zimmerman AL, Orefice LL, Boyle KA, Bai L, Song BJ, Bashista KA, O'Neill TG, Zhuo J, Tsan C, Hoynoski J, Rutlin M, Kus L, Niederkofler V, Watanabe M, Dymecki SM, Nelson SB, Heintz N, Hughes DI, Ginty DD. The Cellular and Synaptic Architecture of the Mechanosensory Dorsal Horn. Cell. 2017 Jan 12;168(1-2):295-310.e19. doi: 10.1016/j.cell.2016.12.010. Epub 2016 Dec 29. PMID: 28041852; PMCID: PMC5236062.
