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Behavioral profile of a heterozygous mutant mouse model for EGF-like domain neuregulin 1.
Behav Neurosci. 2008 Aug; 122(4):748-59.BN

Abstract

Human genetic studies have demonstrated that the neuregulin 1 gene (NRG1) is involved in the development of schizophrenia. Alternative splicing of NRG1 results in at least 15 distinct isoforms and all contain an extracellular epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1's biological activity. Here, we characterize a heterozygous mutant model for mouse EGF-like domain neuregulin 1 (Nrg1) regarding schizophrenia-related behavioral domains. A comprehensive, multitiered phenotyping strategy was used to investigate locomotion, exploration, anxiety-related behaviors, and sensorimotor gating. Nrg1 mutant mice exhibited a hyper-locomotive phenotype and an improved ability to habituate to a new environment. Extensive analysis of anxiety-related behaviors revealed a wild type-like phenotype in this domain. However, a moderate impairment in sensorimotor gating was found after pharmacological challenge using psychoactive substances. Our study adds to the increasing behavioral data available from a variety of animal models for Nrg1 isoforms. We suggest a standardized and comprehensive behavioral phenotyping approach to distinguish between the different models and to clarify their relevance for schizophrenia research. Future behavioral investigations will focus on the negative and cognitive symptoms of schizophrenia.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Duffy L
Schizophrenia Research Institute, Sydney NSW, Australia.
Cappas E
No affiliation info available
Scimone A
No affiliation info available
Schofield PR
No affiliation info available
Karl T
No affiliation info available

MeSH

Acoustic StimulationAdaptation, PhysiologicalAmino Acid MotifsAnimalsBehavior, AnimalCentral Nervous System StimulantsDextroamphetamineDizocilpine MaleateEpidermal Growth FactorExploratory BehaviorGait Disorders, NeurologicHeterozygoteInhibition, PsychologicalLocomotionMaze LearningMiceMice, Inbred C57BLMice, TransgenicModels, BiologicalMotor ActivityMutationNeural InhibitionNeuregulin-1

Pub Type(s)

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

Language

eng

PubMed ID

18729627

Citation

Duffy, Liesl, et al. "Behavioral Profile of a Heterozygous Mutant Mouse Model for EGF-like Domain Neuregulin 1." Behavioral Neuroscience, vol. 122, no. 4, 2008, pp. 748-59.
Duffy L, Cappas E, Scimone A, et al. Behavioral profile of a heterozygous mutant mouse model for EGF-like domain neuregulin 1. Behav Neurosci. 2008;122(4):748-59.
Duffy, L., Cappas, E., Scimone, A., Schofield, P. R., & Karl, T. (2008). Behavioral profile of a heterozygous mutant mouse model for EGF-like domain neuregulin 1. Behavioral Neuroscience, 122(4), 748-59. https://doi.org/10.1037/0735-7044.122.4.748
Duffy L, et al. Behavioral Profile of a Heterozygous Mutant Mouse Model for EGF-like Domain Neuregulin 1. Behav Neurosci. 2008;122(4):748-59. PubMed PMID: 18729627.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Behavioral profile of a heterozygous mutant mouse model for EGF-like domain neuregulin 1. AU - Duffy,Liesl, AU - Cappas,Emily, AU - Scimone,Anna, AU - Schofield,Peter R, AU - Karl,Tim, PY - 2008/8/30/pubmed PY - 2008/11/6/medline PY - 2008/8/30/entrez SP - 748 EP - 59 JF - Behavioral neuroscience JO - Behav Neurosci VL - 122 IS - 4 N2 - Human genetic studies have demonstrated that the neuregulin 1 gene (NRG1) is involved in the development of schizophrenia. Alternative splicing of NRG1 results in at least 15 distinct isoforms and all contain an extracellular epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1's biological activity. Here, we characterize a heterozygous mutant model for mouse EGF-like domain neuregulin 1 (Nrg1) regarding schizophrenia-related behavioral domains. A comprehensive, multitiered phenotyping strategy was used to investigate locomotion, exploration, anxiety-related behaviors, and sensorimotor gating. Nrg1 mutant mice exhibited a hyper-locomotive phenotype and an improved ability to habituate to a new environment. Extensive analysis of anxiety-related behaviors revealed a wild type-like phenotype in this domain. However, a moderate impairment in sensorimotor gating was found after pharmacological challenge using psychoactive substances. Our study adds to the increasing behavioral data available from a variety of animal models for Nrg1 isoforms. We suggest a standardized and comprehensive behavioral phenotyping approach to distinguish between the different models and to clarify their relevance for schizophrenia research. Future behavioral investigations will focus on the negative and cognitive symptoms of schizophrenia. SN - 0735-7044 UR - https://www.unboundmedicine.com/medline/citation/18729627/Behavioral_profile_of_a_heterozygous_mutant_mouse_model_for_EGF_like_domain_neuregulin_1_ DB - PRIME DP - Unbound Medicine ER -