RT Journal Article SR Electronic T1 Deletion of Densin-180 Results in Abnormal Behaviors Associated with Mental Illness and Reduces mGluR5 and DISC1 in the Postsynaptic Density Fraction JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 16194 OP 16207 DO 10.1523/JNEUROSCI.5877-10.2011 VO 31 IS 45 A1 Holly J. Carlisle A1 Tinh N. Luong A1 Andrew Medina-Marino A1 Leslie Schenker A1 Eugenia Khorosheva A1 Tim Indersmitten A1 Keith M. Gunapala A1 Andrew D. Steele A1 Thomas J. O'Dell A1 Paul H. Patterson A1 Mary B. Kennedy YR 2011 UL http://www.jneurosci.org/content/31/45/16194.abstract AB Densin is an abundant scaffold protein in the postsynaptic density (PSD) that forms a high-affinity complex with αCaMKII and α-actinin. To assess the function of densin, we created a mouse line with a null mutation in the gene encoding it (LRRC7). Homozygous knock-out mice display a wide variety of abnormal behaviors that are often considered endophenotypes of schizophrenia and autism spectrum disorders. At the cellular level, loss of densin results in reduced levels of α-actinin in the brain and selective reduction in the localization of mGluR5 and DISC1 in the PSD fraction, whereas the amounts of ionotropic glutamate receptors and other prominent PSD proteins are unchanged. In addition, deletion of densin results in impairment of mGluR- and NMDA receptor-dependent forms of long-term depression, alters the early dynamics of regulation of CaMKII by NMDA-type glutamate receptors, and produces a change in spine morphology. These results indicate that densin influences the function of mGluRs and CaMKII at synapses and contributes to localization of mGluR5 and DISC1 in the PSD fraction. They are consistent with the hypothesis that mutations that disrupt the organization and/or dynamics of postsynaptic signaling complexes in excitatory synapses can cause behavioral endophenotypes of mental illness.