A mouse model expressing recombinase in dopamine transporter-positive neurons

This technology is a mouse model that enables a precise flippase recombination in dopamine transporter (DAT)-expressing neurons that can be used to specifically target and study dopaminergic neurons.

Unmet Need: Reliable and specific mouse models for studying dopaminergic neurons

Engineered mouse models have transformed neuroscience research by enabling cell-type-specific manipulation of gene expression and activity. Cre and flippase recombinases are widely used tools for conditional gene expression and deletion. However, their expression does not always reflect endogenous gene expression and can exhibit transgenerational variability, potentially affecting experimental outcomes.

The Technology: Knock-in mouse for precise flippase-mediated recombination in dopamine transporter-expressing neurons

This technology enables the precise introduction of flippase recombinase in dopamine transporter (DAT)-expressing neurons using a CRISPR-Cas9 gene-editing approach, allowing for the selective targeting of dopaminergic neuronal populations. Histological analyses and whole-cell electrophysiological recordings confirmed the high specificity and validated the excitability profile of this neuronal subpopulation. This model facilitates the investigation of dopaminergic neurons under both physiological and pathological conditions. This technology has been validated in in vivo mouse models.

Applications:

• Mouse model for basal ganglia and dopamine neuron systems
• Combinatorial approach with other models for simultaneous investigation of neuronal populations
• Research tool for neuropsychiatric diseases

Advantages:

• Enables precise flippase recombinase expression in dopaminergic neurons
• Improves specificity compared to existing models
• Allows for intersectional genetic strategies

Lead Inventor:

Rui Costa, D.V.M., Ph.D.

Related Publications:

• Albarran E, Fushiki A, Nelson A, Ng D, Chaimowitz C, Nikoobakht L, Sippy T, Peterka DS, Costa RM. “Generation of knock-in Cre and FlpO mouse lines for precise targeting of striatal projection neurons and dopaminergic neurons.” bioRxiv 2025.06.15.659794

• Fushiki A, Ng D, Lewis ZR, Yadav A, Saraiva T, Hammond LA, Wirblich C, Tasic B, Menon V, Alves da Silva J, Costa RM. “A Vulnerable Subtype of Dopaminergic Neurons Drives Early Motor Deficits in Parkinson’s Disease.” bioRxiv 2024.12.20.629776.

Tech Ventures Reference:

• IR CU26033

• Licensing Contact: Kristin Neuman