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Mutant and Transgenic Tools in Modeling Schizophrenia

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Transgenic and Mutant Tools to Model Brain Disorders

Part of the book series: Neuromethods ((NM,volume 44))

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Abstract

Schizophrenia is thought to be a polygenic disorder that is associated with considerable phenotypic heterogeneity across patients, including variations in age at onset, diagnostic symptoms and subsequent course of illness. Consequently, the generation of incisive mutant models for this disorder faces substantive challenges. The majority of mutant models for schizophrenia relate to putative pathobiological and pharmacological processes and to the functional roles of the increasingly large and diverse array of genes associated with risk for the disorder. The present review considers the application of mutant animal phenotypes to the study of pathobiological and pharmacological mechanisms thought to be relevant for schizophrenia, particularly in terms of dopaminergic and glutamatergic dysfunction, and to an increasing range of candidate susceptibility genes. We also discuss various technological approaches to the generation of such mutants and highlight the diverse methodologies adopted in phenotypic assessment of these models. Finally, we outline the principal challenges to be faced by researchers engaging in the generation and evaluation of mutant models for schizophrenia and consider possible approaches to identify improved models.

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Acknowledgments

The authors’ studies are supported by Science Foundation Ireland, the Health Research Board of Ireland and a grant for promotion of multidisciplinary research projects entitled Translational Research Network on Orofacial Neurological Disorders from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland

    Lieve Desbonnet, Colm M. P. O’Tuathaigh & John L. Waddington

  2. Advanced Research Institute for the Sciences and Humanities, Nihon University, Tokyo, Japan

    Katsunori Tomiyama

  3. Department of Pharmacology and Dental Research Centre, Nihon University School of Dentistry, Tokyo, Japan

    Noriaki Koshikawa

Authors
  1. Lieve Desbonnet
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  2. Katsunori Tomiyama
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  3. Noriaki Koshikawa
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  4. Colm M. P. O’Tuathaigh
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  5. John L. Waddington
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Corresponding author

Correspondence to John L. Waddington .

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  1. School of Medicine, Tulane University, Tulane Ave. 1430, New Orleans, 70112, U.S.A.

    Allan V. Kalueff

  2. E. Pittsburgh Ave. 235, Milwaukee, 53204, U.S.A.

    Carisa L. Bergner

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Desbonnet, L., Tomiyama, K., Koshikawa, N., O’Tuathaigh, C.M.P., Waddington, J.L. (2010). Mutant and Transgenic Tools in Modeling Schizophrenia. In: Kalueff, A., Bergner, C. (eds) Transgenic and Mutant Tools to Model Brain Disorders. Neuromethods, vol 44. Humana Press. https://doi.org/10.1007/978-1-60761-474-6_12

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  • DOI: https://doi.org/10.1007/978-1-60761-474-6_12

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