期刊
BEHAVIOURAL BRAIN RESEARCH
卷 223, 期 2, 页码 336-341出版社
ELSEVIER
DOI: 10.1016/j.bbr.2011.04.051
关键词
Neuregulin 1; Prepulse inhibition; Genetic mouse model; Sensorimotor gating; Schizophrenia
资金
- NSW Health
- Baxter Charitable Foundation
- Alma Hazel Eddy Trust
- National Health and Medical Research Council (NHMRC) [568752]
- National Alliance for Research on Schizophrenia and Depression (Young Investigator Award)
- Sylvia and Charles Viertel Charitable Foundation
- [493301]
Evidence suggests that the heterozygous transmembrane domain mutant mouse model for the schizophrenia candidate gene neuregulin 1 (Nrg1 HET) exhibits a deficit in prepulse inhibition (PPI). However, not all mouse models for Nrg1 exhibit PPI deficits. Thus, our study intended to clarify the severity of the initially described PPI deficit in Nrg1 HET mice. For this, Nrg1 mutant mice and wild type-like littermates of one breeding colony were tested for PPI in four different phenotyping facilities in Australia employing a variety of different PPI protocols with fixed and variable interstimulus intervals (ISIs). Testing mutant and wild type-like mice in three Australian phenotyping facilities using PPI protocols with variable ISIs revealed no effect of mutant transmembrane domain Nrg1 on sensorimotor gating. Changes to the startle response and startle response habituation were site/protocol-specific. The employment of two different PPI protocols at the same phenotyping facility revealed a protocol-dependent and site-specific facilitation of PPI in Nrg1 mutant mice compared to wild type-like mice. In conclusion, the often-noted PPI phenotype of the transmembrane domain Nrg1 mutant mouse model is highly PPI protocol-specific and appears sensitive to the particular conditions of the test laboratory. Our study describes wild type-like PPI under most test conditions and across three different laboratories. The research suggests that analysing one of the alleged hallmarks of animal models for schizophrenia must be done carefully: to obtain reliable PPI data it seems necessary to use more than one particular PPI protocol. (C) 2011 Elsevier B.V. All rights reserved.
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