D1-Cre knock-in mouse for genetic targeting of basal ganglia circuits

This technology is a genetically engineered D1-Cre knock-in mouse line that enables precise, cell-type-specific manipulation of D1 receptor-expressing neurons within the basal ganglia to study motor control and neuropsychiatric disease mechanisms.

Unmet Need: Knock-in mouse model for precise cell type-specific targeting in the basal ganglia

Current transgenic mouse models used to study basal ganglia function often rely on bacterial artificial chromosome (BAC) constructs, which can lead to inconsistent gene expression across generations. These expression mismatches limit experimental precision and can complicate the interpretation of circuit-specific manipulations. A more accurate genetic model is necessary to ensure that gene expression aligns with endogenous regulatory elements, enabling reproducible, cell-type-specific studies of basal ganglia function and dysfunction.

The Technology: Knock-in D1-Cre mouse enabling precise basal ganglia circuit studies

This technology is a knock-in mouse model that uses a CRISPR-Cas9-based strategy to insert a Cre recombinase sequence downstream of the endogenous D1 receptor (Drd1) gene, linked by a T2A self-cleaving peptide to preserve native receptor expression. This results in Cre expression precisely mirroring endogenous D1 receptor expression, enabling specific genetic access to D1 receptor-expressing neurons within the basal ganglia.

This technology has been validated through histological and electrophysiological analyses to confirm recombinase activity and expected physiological properties in D1-expressing neurons.

Applications:

  • Research tool for investigating basal ganglia circuitry and function
  • Model for studying motor control and movement disorders
  • Preclinical tool for evaluating targeted therapies in neuropsychiatric and neurodegenerative diseases
  • Platform for probing dopamine-dependent reinforcement learning and decision-making

Advantages:

  • Precisely replicates endogenous D1 receptor expression patterns
  • Eliminates off-target and variable expression
  • Compatible with Cre-dependent genetic and optogenetic tools

Lead Inventor:

Rui Costa, DVM, Ph.D.

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