Review of studies that have used knockout mice to assess normal function of prion protein under immunological or pathophysiological stress. (July 2014)

• Record Type: Journal Article
• Authors: Onodera, Takashi; Sakudo, Akikazu; Tsubone, Hirokazu; Itohara, Shigeyoshi
• Is Part Of: Microbiology and immunology. Volume 58:Number 7(2014:Jul.)
• Page Start: 361
• Page End: 374
• Publication Date: 2014-07
• Subjects: Microbiology -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Microbiology -- Periodicals; Microbiologie -- Périodiques; Immunologie -- Périodiques; 579
• DOI: 10.1111/1348-0421.12162
• Languages: English
• ISSNs: 0385-5600

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="mim12162-sec-0001" sec-type="section"> <p>Deletion of cellular isoform of prion protein (PrP<sup>C</sup>) increases neuronal predisposition to damage by modulating apoptosis and the negative consequences of oxidative stress. <italic>In vivo</italic> studies have demonstrated that PrP<sup>C</sup>‐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<sup>C</sup> reduces brain damage in rat models of cerebral ischemia. In experimental autoimmune encephalomyelitis, PrP<sup>C</sup>‐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<sup>C</sup> has a potential protective role against inflammatory bowel disease. PrP<sup>C</sup>‐deficient mice demonstrate significantly greater increases in blood glucose concentrations after intraperitoneal injection of glucose than wild‐type mice. Further <italic>in vivo</italic> challenges to PrP gene‐deficient models and conditional knockout models with siRNA and <italic>in vivo</italic> administration of PrP‐ligating agents may assist in refining knowledge of the lymphoid function of PrP<sup>C</sup> and predicting the effects of anti‐PrP treatment on the immune system. Together, these findings indicate that PrP<sup>C</sup> may have multiple neuroprotective and anti‐inflammatory roles, which explains why this protein is so widely expressed.</p> </sec> </abstract>