Mouse Models: Knockouts/Knockins

  • Weihua Huang
  • Wenhao Xu
  • Ming D. Li


There is an enormous initiative to establish the genetic basis for addictive disorders. While forward genetic studies focus on identification of risk factors and protective genes impacting on addictive behaviors of humans and animal models, much effort is devoted to functions of these genes and polymorphisms relevant to substance abuse in reverse genetic studies with gene manipulation in intact organisms. Animal models, particularly the laboratory mouse, offer attractive systems with which scientists can work toward the goal. In this chapter, we introduce the state-of-the-art gene targeting technology in reverse genetics. By using homologous recombination and a well-designed strategy, a gene of special interest in the mouse genome can be eliminated or modified for function alteration on purpose. The resultant mutant animals provide excellent models for subsequent studies of gene function in development, pathophysiology, and behaviors. Various genes relevant to addiction to a variety of drugs of abuse have been examined with knockout, knockin, and conditional gene targeting technologies. Studies in these genetic engineered animal models are starting to yield some converging findings, providing crucial insights into brain regions and genes associated with drug addiction, and speeding up our understanding of the complex neuronal processes involved in these disorders. In addition, these animal models provide important platforms for the development of prevention and intervention strategies targeted at an individual’s specific needs.


Animal model Knockout Knockin Addiction 



The preparation of this book chapter was supported in part by National Institutes of Health grants DA-12844 and DA-13783 to Ming D. Li.


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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Psychiatry and Neurobehavioral SciencesUniversity of VirginiaCharlottesvilleUSA
  2. 2.Department of Microbiology and Gene Targeting & Transgenic FacilityUniversity of VirginiaCharlottesvilleUSA

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