title: Mouse pups lacking collapsin response mediator protein 4 manifest impaired olfactory function and hyperactivity in the olfactory bulb.
abstract: Members of the collapsin response mediator protein (CRMP) family are reported to be involved in the pathogenesis of various neuronal disorders, including schizophrenia and autism. One of them, CRMP4, is reported to participate in aspects of neuronal development, such as axonal guidance and dendritic development. However, no physiological or behavioral phenotypes in Crmp4 knockout (Crmp4-KO) mice have been identified, making it difficult to elucidate the in vivo roles of CRMP4. Focusing on the olfaction process because of the previous study showing strong expression of Crmp4 mRNA in the olfactory bulb (OB) during the early postnatal period, it was aimed to test the hypothesis that Crmp4-KO pups would exhibit abnormal olfaction. Based on measurements of their ultrasonic vocalizations, impaired olfactory ability in Crmp4-KO pups was found. In addition, c-Fos expression, a marker of neuron activity, revealed hyperactivity in the OB of Crmp4-KO pups compared with wild-types following exposure to an odorant. Moreover, the mRNA and protein expression levels of glutamate receptor 1 (GluR1) and 2 (GluR2) were exaggerated in Crmp4-KO pups relative to other excitatory and inhibitory receptors and transporters, raising the possibility that enhanced expression of these excitatory receptors contributes to the hyperactivity phenotype and impairs olfactory ability. This study provides evidence for an animal model for elucidating the roles of CRMP4 in the development of higher brain functions as well as for elucidating the developmental regulatory mechanisms controlling the activity of the neural circuitry.
authors.affiliation: Graduate School of Life Sciences, Toyo University, 1-1-1 Itakura, Oura, Gunma, 374-0193, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Tsutiya
authors.affiliation: Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Masugi
authors.initials: M
authors.lastname: Nishihara
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.affiliation: Graduate School of Life Sciences, Toyo University, 1-1-1 Itakura, Oura, Gunma, 374-0193, Japan.|Bio-Nano Electronic Research Centre, Toyo University, Kawagoe, Saitama, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Ohtani-Kaneko
mesh_terms: D000818:Animals; D004192:Discrimination, Psychological / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009812:Odorants; D009830:Olfactory Bulb / Q000378:metabolism*; D055696:Olfactory Perception / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D014828:Vocalization, Animal
chemical_list: D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D018091:Receptors, AMPA; C526904:Dpysl3 protein, mouse; C104722:glutamate receptor ionotropic, AMPA 2
keywords: GluR1; GluR2; c-Fos expression; olfactory discrimination; ultrasonic vocalization