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Adult mice with reduced Nurr1 expression: an animal model for schizophrenia

Molecular Psychiatry volume 12, pages 756–766 (2007)Cite this article

Abstract

The transcription factor Nurr1 (NR4A2) has been found to play a critical role in the development of midbrain dopaminergic neurons. Nurr1 heterozygous (+/−) male and female mice expressing 35–40% of normal levels of Nurr1 were generated and examined in animal models related to symptoms of schizophrenia. The Nurr1 (+/−) mice displayed hyperactivity in a novel environment, which persisted after administration of the dopamine-mimetic amphetamine and the N-methyl-D-aspartate receptor antagonist phencyclidine. The Nurr1 (+/−) mice were deficient in the retention of emotional memory and showed an enhanced response to swim stress. In addition, Nurr1 (+/−) male mice displayed a reduced dopamine turnover in the striatum and an enhanced dopamine turnover in the prefrontal cortex, while female mice showed an opposite pattern. These results show that Nurr1 (+/−) mice display a pattern of behaviors indicative of potential relevance for symptoms of schizophrenia combined with a gender-specific abnormal dopamine transmission in the striatum and prefrontal cortex, respectively. This suggests that the Nurr1 mutant mouse may be a potential animal model for studies on some of the behavioral and molecular mechanisms underlying schizophrenia.

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Acknowledgements

We thank Norma Serrano and Nather Majid for technical assistance. This study was partially supported by Göran Gustafsson Foundation, Research funds of Karolinska Institute, Swedish Foundation for Strategic Research, The Swedish Research Council and Wallenberg Consortium North.

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Author notes

  1. P Rojas

    Present address: 4Current address: Laboratory of Neurotoxicology, Instituto Nacional de Neurología y Neurocirugía. Av. Insurgentes Sur No. 3877, Col. La Fama C.P. 14269, México D.F., México.,

Authors and Affiliations

  1. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

    P Rojas & S O Ögren

  2. Ludwig Institute for Cancer Research, Karolinska Institutet, Stockholm, Sweden

    E Joodmardi & T Perlmann

  3. AstraZeneca, Södertälje, Sweden

    Y Hong

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  1. P Rojas
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Correspondence to S O Ögren.

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Rojas, P., Joodmardi, E., Hong, Y. et al. Adult mice with reduced Nurr1 expression: an animal model for schizophrenia. Mol Psychiatry 12, 756–766 (2007). https://doi.org/10.1038/sj.mp.4001993

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