Genetic Labeling Reveals Spatial Expression Pattern Of Neuregulin1 In Mouse Brain

Schizophrenia is a severe and disabled chronic psychiatric disorder with a lifetime prevalence of about 1%in the general population and associated with substantial morbidity and mortality as well as personal and societal costs.High heritability,up to 80%,points to a major role for inherited genetic variants in the aetiology of schizophrenia.Recent studies have shown that Neuregulin-1（Nrg1）is a candidate gene for schizophrenia.It is widely recognized that Nrg1 plays a crucial role in regulating peripheral myelinogenesis,interneuronal migration,and function of GABAergic neurotransmitter receptors.However,current studies mostly focused on pharmacological experiments in vitro,and ignored the physiological function of endogenous Nrg1 in various types of cells and expression pattern of endogenous Nrg1in mammals’brain relatively.This paper aims to create the Nrg1-Cre mice via CRISPR/Cas9 system and systematically and generally reveal the expression patterns of Nrg1 gene in mice brain using the methods of immunofluorescence and photoshoot by Leica TCS Confocal,via crossing Nrg1-Cre mice with Ai14 mice to get the Nrg1 reporter mice,or injecting p AAV-EF1a-DIO-td Tomato-WPRE into different areas in the brain of adult Nrg1-Cre^+/-mice.This paper successfully created the novel Nrg1-Cre mice,where Cre expression is under the control of endogenous Nrg1 promoter,and verified their reliability.These mice can be a useful animal model for research of Nrg1 or Nrg1/Erb B pathways.In consideration of the linkage between functions of cortex,hippocampus and striatum and symptoms of schizophrenia,this acticle kept the focus on the Nrg1 expression in cortex,hippocampus and striatum:we found dominant Nrg1 expression in pyramidal neurons in the 2/3 layer of cerebral cortex,as well as some expression in pyramidal neurons in the 5/6 layers of the prefrontal cortex;in the basal ganglia,Nrg1expression was found in the Drd1 positive medium spiny GABAergic neurons projecting to the reticular part of substantia nigra in midbrain,suggesting its function on basal ganglia direct pathway;in addition,we found the Nrg1 gene was expressed in partial granular cells in dentate gyrus projecting to pyramidal neurons in CA3 areas and in partial pyramidal cells in subiculum projecting to mammillary nucleus via fornix,related to hippocampal trisynaptic loop and Papez circuit respectively.These results may provide histological and morphological basis for the subsequent studies of the physiological function of endogenous Nrg1 and explaining the relationship between Nrg1 variation and schizophrenia.