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Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: implications for understanding schizophrenia.
Genes Brain Behav. 2007 Oct; 6(7):677-87.GB

Abstract

Human genetic studies have shown that neuregulin 1 (NRG1) is a potential susceptibility gene for schizophrenia. Nrg1 influences various neurodevelopmental processes, which are potentially related to schizophrenia. The neurodevelopmental theory of schizophrenia suggests that interactions between genetic and environmental factors are responsible for biochemical alterations leading to schizophrenia. To investigate these interactions and to match experimental design with the pathophysiology of schizophrenia, we applied a comprehensive behavioural phenotyping strategy for motor activity, exploration and anxiety in a heterozygous Nrg1 transmembrane domain mutant mouse model (Nrg1 HET) using different housing conditions and age groups. We observed a locomotion- and exploration-related hyperactive phenotype in Nrg1 HETs. Increased age had a locomotion- and exploration-inhibiting effect, which was significantly attenuated in mutant mice. Environmental enrichment (EE) had a stimulating influence on locomotion and exploration. The impact of EE was more pronounced in Nrg1 hypomorphs. Our study also showed a moderate task-specific anxiolytic-like phenotype for Nrg1 HETs, which was influenced by external factors. The behavioural phenotype detected in heterozygous Nrg1 mutant mice is not specific to schizophrenia per se, but the increased sensitivity of mutant mice to exogenous factors is consistent with the pathophysiology of schizophrenia and the neurodevelopmental theory. Our findings reinforce the importance of carefully controlling experimental designs for external factors and of comprehensive, integrative phenotyping strategies. Thus, Nrg1 HETs may, in combination with other genetic and drug models, help to clarify pathophysiological mechanisms behind schizophrenia.

Authors+Show Affiliations

Neuroscience Institute of Schizophrenia and Allied Disorders, Sydney, NSW, Australia. t.karl@garvan.org.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17309661

Citation

Karl, T, et al. "Altered Motor Activity, Exploration and Anxiety in Heterozygous Neuregulin 1 Mutant Mice: Implications for Understanding Schizophrenia." Genes, Brain, and Behavior, vol. 6, no. 7, 2007, pp. 677-87.
Karl T, Duffy L, Scimone A, et al. Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: implications for understanding schizophrenia. Genes Brain Behav. 2007;6(7):677-87.
Karl, T., Duffy, L., Scimone, A., Harvey, R. P., & Schofield, P. R. (2007). Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: implications for understanding schizophrenia. Genes, Brain, and Behavior, 6(7), 677-87.
Karl T, et al. Altered Motor Activity, Exploration and Anxiety in Heterozygous Neuregulin 1 Mutant Mice: Implications for Understanding Schizophrenia. Genes Brain Behav. 2007;6(7):677-87. PubMed PMID: 17309661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: implications for understanding schizophrenia. AU - Karl,T, AU - Duffy,L, AU - Scimone,A, AU - Harvey,R P, AU - Schofield,P R, Y1 - 2007/02/13/ PY - 2007/2/21/pubmed PY - 2007/12/6/medline PY - 2007/2/21/entrez SP - 677 EP - 87 JF - Genes, brain, and behavior JO - Genes Brain Behav VL - 6 IS - 7 N2 - Human genetic studies have shown that neuregulin 1 (NRG1) is a potential susceptibility gene for schizophrenia. Nrg1 influences various neurodevelopmental processes, which are potentially related to schizophrenia. The neurodevelopmental theory of schizophrenia suggests that interactions between genetic and environmental factors are responsible for biochemical alterations leading to schizophrenia. To investigate these interactions and to match experimental design with the pathophysiology of schizophrenia, we applied a comprehensive behavioural phenotyping strategy for motor activity, exploration and anxiety in a heterozygous Nrg1 transmembrane domain mutant mouse model (Nrg1 HET) using different housing conditions and age groups. We observed a locomotion- and exploration-related hyperactive phenotype in Nrg1 HETs. Increased age had a locomotion- and exploration-inhibiting effect, which was significantly attenuated in mutant mice. Environmental enrichment (EE) had a stimulating influence on locomotion and exploration. The impact of EE was more pronounced in Nrg1 hypomorphs. Our study also showed a moderate task-specific anxiolytic-like phenotype for Nrg1 HETs, which was influenced by external factors. The behavioural phenotype detected in heterozygous Nrg1 mutant mice is not specific to schizophrenia per se, but the increased sensitivity of mutant mice to exogenous factors is consistent with the pathophysiology of schizophrenia and the neurodevelopmental theory. Our findings reinforce the importance of carefully controlling experimental designs for external factors and of comprehensive, integrative phenotyping strategies. Thus, Nrg1 HETs may, in combination with other genetic and drug models, help to clarify pathophysiological mechanisms behind schizophrenia. SN - 1601-1848 UR - https://www.unboundmedicine.com/medline/citation/17309661/Altered_motor_activity_exploration_and_anxiety_in_heterozygous_neuregulin_1_mutant_mice:_implications_for_understanding_schizophrenia_ L2 - https://doi.org/10.1111/j.1601-183X.2006.00298.x DB - PRIME DP - Unbound Medicine ER -