Adult mice with reduced Nurr1 expression: an animal model for schizophrenia.
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.
Rojas
P
P
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Joodmardi
E
E
Hong
Y
Y
Perlmann
T
T
Ogren
S O
SO
D000223:Adaptation, Psychological / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006579:Heterozygote; D006948:Hyperkinesis / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D017072:Neostriatum / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D017397:Prefrontal Cortex / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014157:Transcription Factors; D004298:Dopamine