RGD Reference Report - Sex-specific neuroendocrine and behavioral phenotypes in hypomorphic Type II Neuregulin 1 rats. - Rat Genome Database

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Sex-specific neuroendocrine and behavioral phenotypes in hypomorphic Type II Neuregulin 1 rats.

Authors: Taylor, Sara B  Markham, Julie A  Taylor, Adam R  Kanaskie, Brooke Z  Koenig, James I 
Citation: Taylor SB, etal., Behav Brain Res. 2011 Oct 31;224(2):223-32. doi: 10.1016/j.bbr.2011.05.008. Epub 2011 May 19.
RGD ID: 405650204
Pubmed: PMID:21620900   (View Abstract at PubMed)
PMCID: PMC3159843   (View Article at PubMed Central)
DOI: DOI:10.1016/j.bbr.2011.05.008   (Journal Full-text)

Neuregulin 1 (NRG1) is an important growth factor involved in the development and plasticity of the central nervous system. Since its identification as a susceptibility gene for schizophrenia, several transgenic mouse models have been employed to elucidate the role NRG1 may play in the pathogenesis of psychiatric disease. Unfortunately very few studies have included females, despite the fact that some work suggests that the consequences of disrupted NRG1 expression may be sex-specific. Here, we used Nrg1 hypomorphic (Nrg1(Tn)) Fischer rats to demonstrate sex-specific changes in neuroendocrine and behavioral phenotypes as a consequence of reduced Type II NRG1 expression. We have previously shown that male Nrg1(Tn) rats have increased basal corticosterone levels, and fail to habituate to an open field despite normal overall levels of locomotor activity. The current studies show that, in contrast, female Nrg1(Tn) rats exhibit enhanced suppression of corticosterone levels following an acute stress, reduced locomotor activity, and enhanced habituation to novel environments. Furthermore, we also show that female, but not male, Nrg1(Tn) rats have impaired prepulse inhibition. Finally, we provide evidence that sex-specific changes are not likely attributable to major disruptions in the hypothalamic-pituitary-gonadal axis, as measures of pubertal onset, estrous cyclicity, and reproductive capacity were unaltered in female Nrg1(Tn) rats. Our results provide further support for both the involvement of NRG1 in the control of hypothalamic-pituitary-adrenal axis function and the sex-specific nature of this relationship.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
F344-Nrg1Tn(sb-T2/Bart3)2.183McwiRatabnormal habituation  IMP  RGD 
Nrg1Ratabnormal habituation  IMP  RGD 
Nrg1Tn(sb-T2/Bart3)2.183McwiRatabnormal habituation  IMP  RGD 
F344-Nrg1Tn(sb-T2/Bart3)2.183McwiRatdecreased locomotor activity sexual_dimorphismIMP compared to mutant maleRGD 
Nrg1Ratdecreased locomotor activity sexual_dimorphismIMP compared to mutant maleRGD 
Nrg1Tn(sb-T2/Bart3)2.183McwiRatdecreased locomotor activity sexual_dimorphismIMP compared to mutant maleRGD 
F344-Nrg1Tn(sb-T2/Bart3)2.183McwiRatdecreased prepulse inhibition sexual_dimorphismIMP compared to wild type femaleRGD 
Nrg1Ratdecreased prepulse inhibition sexual_dimorphismIMP compared to wild type femaleRGD 
Nrg1Tn(sb-T2/Bart3)2.183McwiRatdecreased prepulse inhibition sexual_dimorphismIMP compared to wild type femaleRGD 
F344-Nrg1Tn(sb-T2/Bart3)2.183McwiRatincreased startle reflex sexual_dimorphismIAGP compared to femaleRGD 
F344/NCrlRatincreased startle reflex sexual_dimorphismIAGP compared to femaleRGD 
Nrg1Ratincreased startle reflex sexual_dimorphismIAGP compared to femaleRGD 
Nrg1Tn(sb-T2/Bart3)2.183McwiRatincreased startle reflex sexual_dimorphismIAGP compared to femaleRGD 
Objects Annotated

Genes (Rattus norvegicus)
Nrg1  (neuregulin 1)
Nrg1Tn(sb-T2/Bart3)2.183Mcwi  (neuregulin 1; transposon insertion 2.183, Medical College of Wisconsin)


Additional Information