title: Deletion of olfactomedin 2 induces changes in the AMPA receptor complex and impairs visual, olfactory, and motor functions in mice.
abstract: Olfactomedin 2 (Olfm2) is a secretory glycoprotein belonging to the family of olfactomedin domain-containing proteins. A previous study has shown that a mutation in OLFM2 is associated with primary open angle glaucoma in Japanese patients. In the present study, we generated Olfm2 deficient mice by replacing the Olfm2 gene with the LacZ gene. The loss of Olfm2 resulted in no gross abnormalities. However, Olfm2 null mice showed reduced exploration, locomotion, olfactory sensitivity, abnormal motor coordination, and anxiety related behavior. The pattern of the Olfm2 gene expression was studied in the brain and eye using β-galactosidase staining. In the brain, Olfm2 was mainly expressed in the olfactory bulb, cortex, piriform cortex, olfactory trabeculae, and inferior and superior colliculus. In the eye expression was detected mainly in retinal ganglion cells. In Olfm2 null mice, the amplitude of the first negative wave in the visual evoked potential test was significantly reduced as compared with wild-type littermates. Olfm2, similar to Olfm1, interacted with the GluR2 subunit of the AMPAR complexes and Olfm2 co-segregated with the AMPA receptor subunit GluR2 and other synaptic proteins in the synaptosomal membrane fraction upon biochemical fractionation of the adult mice cortex and retina. Immunoprecipitation from the synaptosomal membrane fraction of the Olfm2 null mouse brain cortex using the GluR2 antibody showed reduced levels of several components of the AMPAR complex in the immunoprecipitates including Olfm1, PSD95 and CNIH2. These results suggest that heterodimers of Olfm1 and Olfm2 interact with AMPAR more efficiently than Olfm2 homodimers and that Olfm2 plays a role in the organization of the AMPA receptor complexes.
authors.affiliation: Section on Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: sultanaa@nei.nih.gov.
authors.forename: Afia
authors.initials: A
authors.lastname: Sultana
authors.affiliation: Section on Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: nakayan@nei.nih.gov.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakaya
authors.affiliation: Genetic Engineering Facility, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: Lijin.Dong@nih.gov.
authors.forename: Lijin
authors.initials: L
authors.lastname: Dong
authors.affiliation: Histopathology Core Facility, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: mones@nei.nih.gov.
authors.forename: Mones
authors.initials: M
authors.lastname: Abu-Asab
authors.affiliation: Visual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: qianh@nei.nih.gov.
authors.forename: Haohua
authors.initials: H
authors.lastname: Qian
authors.affiliation: Section on Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: tomarevs@nei.nih.gov.
authors.forename: Stanislav I
authors.initials: SI
authors.lastname: Tomarev
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D005074:Evoked Potentials, Visual / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000235:genetics; D006023:Glycoproteins / Q000172:deficiency* / Q000235:genetics; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009069:Movement Disorders / Q000235:genetics*; D000857:Olfaction Disorders / Q000235:genetics*; D009900:Optic Nerve / Q000473:pathology; D018091:Receptors, AMPA / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*; D014786:Vision Disorders / Q000150:complications / Q000235:genetics*
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D018091:Receptors, AMPA; C081451:olfactomedin
keywords: AMPA receptor; Anxiety behavior; Mouse; Neurobiology; Olfactomedin 2; Olfactory defects; Retina