Intranasal injection of H129ΔTK-TT recombinant virus into OMP-Cre mice was performed by slow instillation through one nostril in anaesthetized animals. Intraocular (vitreal) injection of virus into anaesthetized PCP2/L7-Cre mice was performed by scleral puncture. Injection of virus into the cerebellum was carried out under deep anesthesia using
a sterotaxic frame. Mice were monitored daily for Selleck LY2109761 the development of symptoms: mild symptoms included a slightly hunched back and increased anxiety; more severe symptoms (indicative of more widespread viral infection) included an ungroomed coat, weight loss, and nasal or lacrimal excretions. Mice showing such severe symptoms were immediately euthanized by cardiac perfusion, and brain tissue was collected for histological analysis by cryo-sectioning. tdTomato expression was visualized by native fluorescence, while other markers (NeuN, GFAP, etc.) were detected by immunohistochemistry. Further details are provided in Supplemental Experimental Procedures. We thank Dr. L. Enquist for the H129 strain of HSV1, advice, and encouragement throughout this project and for feedback on the
manuscript, Dr. Jerry Weir for plasmid pGAL10, Dr. Joseph Gogos for OMP-Cre mice, Dr. Markus Meister for help with visual system circuitry, Drs. A. Basbaum and E. Callaway for helpful comments on the manuscript, G. Mosconi and H. Oates-Barker for laboratory management, and NVP-AUY922 nmr G. Mancuso for administrative assistance. This work was supported by NIH grant 1RO1MH070053. D.J.A. is an Investigator of the Howard Hughes Medical Institute. “
disorder (BD, also known as manic-depressive illness) is a severe mood disorder consisting of episodes of mania and depression. The lifetime prevalence of bipolar disorder in the general population is ∼1% and the illness is associated with considerable morbidity and a high lifetime risk of suicide (Merikangas et al., 2011). Genes play an important role in risk for ADAMTS5 BD. The rate of concordance for monozygotic twins is 40%, compared with a 5% rate in dizygotic twins (Kendler et al., 1995, Kieseppä et al., 2004 and McGuffin et al., 2003), and risk among the first-degree relatives of individuals with BD is ten-fold greater than risk among the general population (Barnett and Smoller, 2009). However, as with other psychiatric disorders, the genetics of BD is complex, probably due to a high degree of genetic heterogeneity and considerable phenotypic heterogeneity of clinical populations (Potash et al., 2007). Genetic risk factors with individually large effects are likely to be rare. Association-based methods to identify common genetic risk alleles in BD have met with limited success. Early studies implicated a few common variants with modest effects (Baum et al., 2008 and Ferreira et al., 2008).