• Media type: E-Article
  • Title: Genetically modified pig models for neurodegenerative disorders
  • Contributor: Holm, Ida E; Alstrup, Aage Kristian Olsen; Luo, Yonglun
  • imprint: Wiley, 2016
  • Published in: The Journal of Pathology
  • Language: English
  • DOI: 10.1002/path.4654
  • ISSN: 0022-3417; 1096-9896
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Increasing incidence of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease has become one of the most challenging health issues in ageing humans. One approach to combat this is to generate genetically modified animal models of neurodegenerative disorders for studying pathogenesis, prognosis, diagnosis, treatment, and prevention. Owing to the genetic, anatomic, physiologic, pathologic, and neurologic similarities between pigs and humans, genetically modified pig models of neurodegenerative disorders have been attractive large animal models to bridge the gap of preclinical investigations between rodents and humans. In this review, we provide a neuroanatomical overview in pigs and summarize and discuss the generation of genetically modified pig models of neurodegenerative disorders including Alzheimer's diseases, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, and ataxia–telangiectasia. We also highlight how non‐invasive bioimaging technologies such as positron emission tomography (<jats:styled-content style="fixed-case">PET</jats:styled-content>), computer tomography (<jats:styled-content style="fixed-case">CT</jats:styled-content>), and magnetic resonance imaging (<jats:styled-content style="fixed-case">MRI</jats:styled-content>), and behavioural testing have been applied to characterize neurodegenerative pig models. We further propose a multiplex genome editing and preterm recloning (<jats:styled-content style="fixed-case">MAP</jats:styled-content>) approach by using the rapid growth of the ground‐breaking precision genome editing technology <jats:styled-content style="fixed-case">CRISPR</jats:styled-content>/Cas9 and somatic cell nuclear transfer (<jats:styled-content style="fixed-case">SCNT</jats:styled-content>). With this approach, we hope to shorten the temporal requirement in generating multiple transgenic pigs, increase the survival rate of founder pigs, and generate genetically modified pigs that will more closely resemble the disease‐causing mutations and recapitulate pathological features of human conditions. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.</jats:p>