Pharmacological perturbation reveals deficits in D2 receptor responses in Thap1 null mice

Natalie M. Frederick, Morgan M. Pooler, Parth Shah, Alessandro Didonna, Puneet Opal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The primary dystonia DYT6 is caused by mutations in the transcription factor Thanatos-associated protein 1 (THAP1). To understand THAP1’s functions, we generated mice lacking THAP1 in the nervous system. THAP1 loss causes locomotor deficits associated with transcriptional changes. Since many of the genes misregulated involve dopaminergic signaling, we pharmacologically challenged the two striatal canonical dopamine pathways: the direct, regulated by the D1 receptor, and the indirect, regulated by the D2 receptor. We discovered that depleting THAP1 specifically interferes with the D2 receptor responses, pointing to a selective misregulation of the indirect pathway in DYT6 with implications for pathogenesis and treatment.

Original languageEnglish (US)
Pages (from-to)2302-2308
Number of pages7
JournalAnnals of clinical and translational neurology
Issue number12
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


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