Skip to Content
Merck
  • Neuregulin 1 expression and electrophysiological abnormalities in the Neuregulin 1 transmembrane domain heterozygous mutant mouse.

Neuregulin 1 expression and electrophysiological abnormalities in the Neuregulin 1 transmembrane domain heterozygous mutant mouse.

PloS one (2015-05-21)
Leonora E Long, Paul Anderson, Elisabeth Frank, Alex Shaw, Shijie Liu, Xu-Feng Huang, Didier Pinault, Tim Karl, Terence J O'Brien, Cynthia Shannon Weickert, Nigel C Jones
ABSTRACT

The Neuregulin 1 transmembrane domain heterozygous mutant (Nrg1 TM HET) mouse is used to investigate the role of Nrg1 in brain function and schizophrenia-like behavioural phenotypes. However, the molecular alterations in brain Nrg1 expression that underpin the behavioural observations have been assumed, but not directly determined. Here we comprehensively characterise mRNA Nrg1 transcripts throughout development of the Nrg1 TM HET mouse. In addition, we investigate the regulation of high-frequency (gamma) electrophysiological oscillations in this mutant mouse to associate molecular changes in Nrg1 with a schizophrenia-relevant neurophysiological profile. Using exonic probes spanning the cysteine-rich, epidermal growth factor (EGF)-like, transmembrane and intracellular domain encoding regions of Nrg1, mRNA levels were measured using qPCR in hippocampus and frontal cortex from male and female Nrg1 TM HET and wild type-like (WT) mice throughout development. We also performed electrophysiological recordings in adult mice and analysed gamma oscillatory at baseline, in responses to auditory stimuli and to ketamine. In both hippocampus and cortex, Nrg1 TM HET mice show significantly reduced expression of the exon encoding the transmembrane domain of Nrg1 compared with WT, but unaltered mRNA expression encoding the extracellular bioactive EGF-like and the cysteine-rich (type III) domains, and development-specific and region-specific reductions in the mRNA encoding the intracellular domain. Hippocampal Nrg1 protein expression was not altered, but NMDA receptor NR2B subunit phosphorylation was lower in Nrg1 TM HET mice. We identified elevated ongoing and reduced sensory-evoked gamma power in Nrg1 TM HET mice. We found no evidence to support the claim that the Nrg1 TM HET mouse represents a simple haploinsufficient model. Further research is required to explore the possibility that mutation results in a gain of Nrg1 function.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium chloride solution, BioUltra, Molecular Biology, ~5 M in H2O
Sigma-Aldrich
Sodium chloride, meets analytical specification of Ph. Eur., BP, USP, 99.0-100.5%
Sigma-Aldrich
Sodium chloride-35Cl, 99 atom % 35Cl
Sigma-Aldrich
Sodium chloride, random crystals, 99.9% trace metals basis
Sigma-Aldrich
Sodium chloride, AnhydroBeads, −10 mesh, 99.999% trace metals basis
Sigma-Aldrich
Sodium chloride, tablet
SAFC
Sodium chloride solution, 5 M
Sigma-Aldrich
Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
Sigma-Aldrich
Goat Anti-Rabbit IgG Antibody, Peroxidase Conjugated, 1 mg/mL (after reconstitution), Chemicon®
Sigma-Aldrich
Sodium chloride solution, 0.85%
Sigma-Aldrich
Glycerol solution, 83.5-89.5% (T)
Sigma-Aldrich
Sodium chloride solution, 0.9% in water, BioXtra, suitable for cell culture
Sigma-Aldrich
Sodium chloride, 99.999% trace metals basis
Sigma-Aldrich
Sodium chloride solution, 5 M in H2O, BioReagent, Molecular Biology, suitable for cell culture
Sigma-Aldrich
Sodium chloride, BioXtra, ≥99.5% (AT)
Sigma-Aldrich
Sodium chloride, BioUltra, Molecular Biology, ≥99.5% (AT)
Sigma-Aldrich
Sodium chloride, Molecular Biology, DNase, RNase, and protease, none detected, ≥99% (titration)
Sigma-Aldrich
Sodium chloride, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%
Sigma-Aldrich
Sodium chloride, BioPerformance Certified, ≥99% (titration), suitable for insect cell culture, suitable for plant cell culture
Sigma-Aldrich
Sodium chloride solution, 5 M
Sigma-Aldrich
Glycerol, BioUltra, Molecular Biology, anhydrous, ≥99.5% (GC)
Sigma-Aldrich
N-Methyl-D-aspartic acid, ≥98% (TLC), solid
Sigma-Aldrich
Glycerol, FCC, FG
Sigma-Aldrich
Glycerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)
Sigma-Aldrich
Glycerin, meets USP testing specifications
Sigma-Aldrich
Glycerol, BioXtra, ≥99% (GC)
Sigma-Aldrich
Glycerol, Molecular Biology, ≥99.0%
Sigma-Aldrich
Glycerol, ≥99.5%
Sigma-Aldrich
Sodium deoxycholate, BioXtra, ≥98.0% (dry matter, NT)
Sigma-Aldrich
Sodium deoxycholate, ≥97% (titration)