Behavioral profile of a heterozygous mutant mouse model for EGF-like domain neuregulin 1.
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.
Duffy
Liesl
L
Schizophrenia Research Institute, Sydney NSW, Australia.
Cappas
Emily
E
Scimone
Anna
A
Schofield
Peter R
PR
Karl
Tim
T
D000161:Acoustic Stimulation / Q000379:methods; D000222:Adaptation, Physiological / Q000235:genetics; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000235:genetics*; D005106:Exploratory Behavior / Q000502:physiology; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000235:genetics; D006579:Heterozygote; D007266:Inhibition, Psychological; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009154:Mutation / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects; D020890:Neuregulin-1 / Q000235:genetics*
D000697:Central Nervous System Stimulants; D020890:Neuregulin-1; D004815:Epidermal Growth Factor; D016291:Dizocilpine Maleate; D003913:Dextroamphetamine