# Characterization of a DRD2 Variant that is Associated With a Movement Disorder

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $345,021

## Abstract

Project Summary
Dopamine receptors are the primary therapeutic targets for a variety of neurological and psychiatric disorders,
including schizophrenia, Parkinson's disease, and many other movement disorders. The five subtypes of
dopamine receptors (D1-D5) are members of the superfamily of G protein-coupled receptors. This proposal is
focused on the D2 receptor and, in particular, on the functional consequences of a novel DRD2 allelic variant
that is linked to a movement disorder in at least one pedigree. The two Aims will test the hypotheses that the
putatively pathogenic variant will exhibit altered signaling and cell surface expression compared to the
reference D2 receptor when expressed in a neuronal cell line (Aim 1) or in dopamine neurons in mouse brain
(Aim 2a), and that mice expressing the novel variant will exhibit motor impairments consistent with the human
phenotype (Aim 2b). In Aim 1 we will determine if the impaired recruitment of arrestin and enhanced activation
of G proteins observed when expressed in human embryonic kidney 293 cells is also characteristic of the novel
variant when expressed in a neuronal cell line. In Aim 2 we will create a knock-in mouse model of homozygous
and heterozygous expression of the putatively pathogenic variant. We will evaluate the functional properties of
the novel variant in midbrain dopamine neurons using slice electrophysiology, and conduct analyses of
behaviors that are thought to model the human clinical condition. In addition, D2 receptor expression will be
quantified in midbrain and neostriatum of the knock-in mouse. The aims proposed here will quantify the effect
of this novel polymorphism on the function and expression of the D2 receptor in neuronal cells and in mouse
brain and should provide a biological explanation for manifestation of neurological dysfunction in humans with
this variant.

## Key facts

- **NIH application ID:** 10029640
- **Project number:** 1R21NS117713-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** KIM Arthur NEVE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,021
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10029640

## Citation

> US National Institutes of Health, RePORTER application 10029640, Characterization of a DRD2 Variant that is Associated With a Movement Disorder (1R21NS117713-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10029640. Licensed CC0.

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