title: Review of studies that have used knockout mice to assess normal function of prion protein under immunological or pathophysiological stress.
abstract: Deletion of cellular isoform of prion protein (PrP(C)) increases neuronal predisposition to damage by modulating apoptosis and the negative consequences of oxidative stress. In vivo studies have demonstrated that PrP(C)-deficient mice are more prone to seizure, depression, and induction of epilepsy and experience extensive cerebral damage following ischemic challenge or viral infection. In addition, adenovirus-mediated overexpression of PrP(C) reduces brain damage in rat models of cerebral ischemia. In experimental autoimmune encephalomyelitis, PrP(C)-deficient mice reportedly have a more aggressive disease onset and less clinical improvement during the chronic phase than wild-type mice mice. In mice given oral dextran sulfate, PrP(C) has a potential protective role against inflammatory bowel disease. PrP(C)-deficient mice demonstrate significantly greater increases in blood glucose concentrations after intraperitoneal injection of glucose than wild-type mice. Further in vivo challenges to PrP gene-deficient models and conditional knockout models with siRNA and in vivo administration of PrP-ligating agents may assist in refining knowledge of the lymphoid function of PrP(C) and predicting the effects of anti-PrP treatment on the immune system. Together, these findings indicate that PrP(C) may have multiple neuroprotective and anti-inflammatory roles, which explains why this protein is so widely expressed.
authors.affiliation: Research Center for Food Safety, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657.
authors.forename: Takashi
authors.initials: T
authors.lastname: Onodera
authors.forename: Akikazu
authors.initials: A
authors.lastname: Sakudo
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tsubone
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002545:Brain Ischemia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018188:Cardiovirus Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003863:Depression / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004827:Epilepsy / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D055786:Gene Knockout Techniques; D006801:Humans; D007109:Immunity / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011328:Prions / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D013312:Stress, Physiological
chemical_list: D011328:Prions
keywords: depression; epilepsy; neuroprotection; prion protein