Knock-in mouse lines to target striatal projection neurons and dopaminergic neurons

This technology is the generation of knock-in mouse lines to target striatal projection neurons and dopaminergic neurons.

Unmet Need: Cell type-specific method to study basal ganglia and midbrain dopaminergic system

The basal ganglia and midbrain dopaminergic systems are highly involved in motor control, reward processing, and decision-making and play a crucial role in neuropsychiatric and neurodegenerative disorders. Traditional transgenic approaches to study these systems do not always match the endogenous gene expression and can exhibit transgenerational expression differences. When studying brain systems such as the basal ganglia, small changes in gene expression can impact their function. Therefore, a more targeted approach is necessary to specifically investigate these brain systems.

The Technology: Knock-in mouse lines targeting neurons in the basal ganglia and dopaminergic system

This technology is the generation of knock-in Cre and FlpO mouse lines that target striatal projection neurons and dopaminergic neurons. The knock-in mouse lines were engineered for precise Cre- or FlpO-mediated recombination in dopamine D1 receptor-expressing spiny projection neurons, adenosine A2a receptor-expressing SPNs, and dopamine transporter-expressing neurons in the midbrain. Histological analyses and whole-cell electrophysiological recordings were utilized to validate the specificity and targeting of the mouse lines and intrinsic excitability of the neuronal subpopulations. As such, this technology offers high specificity and reliability for studying basal ganglia and midbrain dopaminergic systems, and can enhance investigations in neuropsychiatric and neurodegenerative diseases.

This technology has been validated in mice.

Applications:

• Research tool to study the basal ganglia and dopaminergic systems
• Research tool to study dopamine-driven reinforcement learning and motor control
• Research tool to study neurodegenerative diseases
• Research tool to study neuropsychiatric diseases

Advantages:

• High precision
• Endogenous expression
• High specificity
• Access to cellular populations during development

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.” eLife 2025 Oct 9.

Tech Ventures Reference:

• IR CU26031

• Licensing Contact: Kristin Neuman