Behavioural characterization of neuregulin 1 type I overexpressing transgenic mice.

Department of Psychiatry, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Neuroreport (Impact Factor: 1.64). 11/2009; 20(17):1523-8. DOI: 10.1097/WNR.0b013e328330f6e7
Source: PubMed

ABSTRACT Neuregulin 1 (NRG1) is a pleiotropic growth factor involved in diverse aspects of brain development and function. In schizophrenia, expression of the NRG1 type I isoform is selectively increased. However, virtually nothing is known about the roles of this isoform in brain. We have studied transgenic mice overexpressing type I NRG1(NRG1type 1-tg) using a series of behavioural tests. NRG1(type 1-tg) mice have a tremor, are impaired on the accelerating rotarod, and have reduced prepulse inhibition in the context of an increased baseline startle response. There is no overall anxiety or activity phenotype, although female NRG(1type 1-tg) mice show mild increases in anxiety on some measures. The pattern of results shows both similarities and differences to those reported in hypomorphic NRG1 mice, and may be relevant for interpreting the increased NRG1 type I expression observed in schizophrenia.

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Available from: Amanda Law, Jul 23, 2014
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    • "This supports findings recently published by the group of Matthew (Davies et al., 2012) demonstrating that the genomewide variety between promoter methylation variance across tissues is less than expected. Additionally, nonparametric correlation analysis revealed a highly significant correlation between blood and PFC (r = 0.195, p b 0.001) as well as with averaged PPI measurements (r = 0.308, p b 0.001), thereby reaffirming the hypothesis of NRG1 overexpression contributing to the schizophrenia phenotype (Deakin et al., 2009). We also observed a weak correlation of blood and dHIP methylation (r = 0.025, p = 0.025) which may be neglected due to its weak coefficient (Supplementary Table S5). "
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    Schizophrenia Research 07/2013; 150(1). DOI:10.1016/j.schres.2013.07.012 · 4.43 Impact Factor
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    • "These transgenic animal models have targeted mutiple mutations in NRG1 genes and the proteolytic processing and cleavage of NRG1 proteins, including mutation or deletion of the Iglike domain (Rimer et al. 2005), TMN domain (NrgTM) (Chesworth et al. 2012; Karl et al. 2007; O'Tuathaigh et al. 2007; Stefansson et al. 2002), type I (Deakin et al. 2009) and type III of NRG1 (Chen et al. 2008), Aph1B/C-γ-secretase (Dejaegere et al. 2008), and BACE1 (Savonenko et al. 2008). It is worth noting that animals with either reduced (O'Tuathaigh et al. 2010; van den Buuse et al. 2009) or excessive expression (Deakin et al. 2009; Kato et al. 2010) of the NRG1 gene showed similar behavioural deficits. Recently, a knock-out mouse model with ErbB4 ablation specifically in the parvalbumin (PV)positive interneurones (PV-ErbB4−/−) was reported to exhibit schizophrenia-relevant phenotypes similar to those observed in NRG1 or ErbB4-null mutant mice (Chen et al. 2010a; Wen et al. 2010). "
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    • "Unaltered ASR PPI deficit; reversible by acute nicotine treatment Type I Nrg1 overexpression (C57BL/6); males and females [29] "
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