Targeted knock-in mouse line for studying neuropsychiatric disease

This technology is a knock-in mouse line targeting a specific population of spiny projection neurons that express the adenosine A2a receptor, enabling the study of motor control, reward, and neuropsychiatric diseases.

Unmet Need: Highly specific mouse line for studying basal ganglia circuitry

Current methods for studying dopaminergic and basal ganglia circuitry rely on pharmacological manipulation and viral expression methods, which are not always precise enough to target a specific cell type or brain region. This limits the ability of researchers to attribute functional and behavioral observations to specific neural populations. Developing strategies for targeting specific neural populations in the basal ganglia is imperative for generating mechanistic insights into how such populations contribute to behavior and neuropsychiatric disease.

The Technology: Knock-in mouse line for precisely targeting a specific neuron population using endogenous expression

This technology is a genetically engineered knock-in mouse line that targets the A2a receptor promoter region, allowing genetic access to neurons that endogenously express the A2a receptor. This technology utilizes CRISPR-Cas9 technology to achieve this endogenous effect, enabling the precise manipulation and labeling of the A2a receptor neuron population in laboratory settings. As such, this mouse line can be used to study neuropsychiatric disease states involving the A2a receptor and for drug validation studies that target the A2a receptor.

This technology has been validated in mice by ensuring accurate and restricted expression in the expected neural populations.

Applications:

  • Research tool for studying basal ganglia circuitry and dopaminergic systems
  • Drug screening and discovery for validating therapeutics targeting the A2a receptor
  • Preclinical modeling of motor control diseases and neuropsychiatric disorders

Advantages:

  • High cell-type specificity for specific striatal neuron populations
  • Limited functional and physiological consequences in targeted cells
  • Compatible with current Cre-dependent tools
  • Utilizes CRISPR-Cas9 to target endogenous genetic promoters
  • Reduces off-target expression and side effects

Lead Inventor:

Rui Costa, DVM, Ph.D.

Related Publications:

Tech Ventures Reference: