Dopamine pp 181-200

Part of the Methods in Molecular Biology book series (MIMB, volume 964) | Cite as

A Molecular Genetic Approach to Uncovering the Differential Functions of Dopamine D2 Receptor Isoforms

Protocol

Abstract

Alterations in the activity of the dopamine D2 receptor (D2R) have been implicated in several neurological and psychiatric disorders, including schizophrenia, Parkinson’s disease, Huntington’s disease, Tourette syndrome, attention-deficit hyperactivity disorder (ADHD), and drug addiction. Two isoforms of D2R, long form (D2LR) and short form (D2SR), have been identified. The specific function of each D2R isoform is poorly understood, primarily because isoform-selective pharmacological agents are not available. Using homologous recombination, we have generated D2LR knockout (KO) mice. D2LR KO mice are completely deficient in D2LR, but still express functional D2SR at a level similar to the total D2R level in wild-type (WT) mice. D2LR is generally the predominant isoform expressed in WT mice. We showed that D2LR KO mice displayed a number of robust behavioral phenotypes distinct from WT mice, indicating that D2LR and D2SR have differential functions. In this chapter we describe the generation and characterization of the D2LR KO mouse. This genetic approach provides a valuable research tool to investigate the functional role of individual D2R isoforms in the mammalian central nervous system (CNS).

Key words

Dopamine D2 receptor Knockout mouse Homologous recombination Transfection of embryonic stem cell Genotyping 

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Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  1. 1.Department of Pharmacology, College of Medicine, Beckman Institute for Advanced Science and TechnologyUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Department of Laboratory Animal ScienceKitasato University School of MedicineKanagawaJapan
  3. 3.Department of NeurologyHospital of University of PennsylvaniaPhiladelphiaUSA

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