Article

Neuregulin-1 immunoglobulin-like domain mutant mice: Clozapine sensitivity and impaired latent inhibition

Department of Psychology, University of Texas at Austin, Austin, Texas, United States
Neuroreport (Impact Factor: 1.64). 03/2005; 16(3):271-5. DOI: 10.1097/00001756-200502280-00014
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ABSTRACT Genetic and behavioral studies in humans and mouse mutants have implicated the gene encoding neuregulin-1 (Nrg-1) as a candidate susceptibility gene for schizophrenia. We examined the behavior of mice heterozygous for a mutation in neuregulin-1's immunoglobulin (Ig)-like domain (Ig-nrg-1 mice). We found that these animals displayed behaviors related to a schizophrenia-like phenotype, such as clozapine suppression of open-field and running wheel activity and impaired latent inhibition. Contrary to findings with other nrg-1 mutants, Ig-nrg-1 mice did not exhibit significantly elevated locomotion relative to littermate controls. These results suggest that Ig-Nrg-1's contribute to some - but not all - aspects of the schizophrenia-like phenotype of nrg-1 mutants, and further support nrg-1 as a candidate gene for schizophrenia.

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Available from: F. Gonzalez-Lima, Jun 08, 2015
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    • "With respect to phenotypic comparisons with more isoform-specific NRG1 deletions, type III NRG1 mutants show greater PPI impairment relative to TM-NRG1 mutants (Chen et al., 2008b). Mutants with targeted disruption of type I/type II NRG1 do not show a hyperactive phenotype (Chen et al., 2007; Rimer et al., 2005). Mutants with partial deletion in the EGF-like domain (pan-isoform) demonstrated a transitory increase in locomotor activity, and more rapid habituation, of exploration in a novel environment. "
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    ABSTRACT: Mutant mice play an increasingly important role in understanding disease processes at multiple levels. In particular, they illuminate the impact of risk genes for disease on such processes. This article reviews recent advances in the application of mutant mice to study the intricacies of dopaminergic (DAergic) function in relation to the putative pathophysiology of psychotic illness, particularly schizophrenia, and antipsychotic drug action. It considers models for understanding the role(s) of risk genes, with a particular focus on DTNBP1 and NRG1, their interactions with environmental factors, and with each other (epistasis). In overview, it considers new schemas for understanding psychotic illness that integrate DAergic pathophysiology with developmental, social, and cognitive processes, and how mutant mouse models can reflect and inform on such schemas.
    Progress in brain research 01/2014; 211:79-112. DOI:10.1016/B978-0-444-63425-2.00004-0 · 5.10 Impact Factor
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    • "The NRG1 SNP8NRG221533 (rs35753505) has most widely been evaluated in relation to cognition (Kurnianingsih et al., 2011). A role for NRG1 in SZ has also been supported by animal studies using NRG1 and ErbB4 mutant mice (Gerlai et al., 2000; Stefansson et al., 2002; Bao et al., 2003; Corfas et al., 2004; Steinthorsdottir et al., 2004; Gu et al., 2005; Rimer et al., 2005), which exhibit behaviors similar to those of established rodent models of SZ (Lipska, 2004). NRG1 polymorphisms have been proposed as risk factors for several other common disorders, including Alzheimer's disease (Chaudhury et al., 2003; Go et al., 2005); epilepsy (early myoclonic encephalopathy; Backx et al., 2009), stroke (Shyu et al., 2004; Xu et al., 2004) breast cancer (Raj et al., 2001), multiple sclerosis (Cannella et al., 1999; Viehover et al., 2001), bipolar disorder (Thomson et al., 2007; Goes et al., 2008; Prata et al., 2009; Walker et al., 2010; Moon et al., 2011) and Hirschsprung Disease (Garcia-Barcelo et al., 2009; Tang et al., 2011). "
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    • "EGF-like domain of Nrg1 (C57BL/6 X 129); Females [32] Unaltered ASR No PPI deficit EGF-like domain of Nrg1 (C57BL/6 X 129/SVEV); males [33] ASR not investigated PPI not investigated Immunoglobulin-like domain Nrg1 (129/SV); males [35] ASR not investigated PPI not investigated Cysteine-rich domain Nrg1 (C57BL/6); Sex not specified [36] ASR not investigated PPI not investigated Type I Nrg1 over-expression (background not described); sex not specified [34] ASR not investigated PPI not investigated Type III Nrg1 over-expression (background not described); sex not specified [34] ASR not investigated PPI not investigated Type III Nrg1 (C57BL/6 X 129); males [28] "
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