Animal Model for Leigh Syndrome

Methods Mol Biol. 2019;2011:451-464. doi: 10.1007/978-1-4939-9554-7_27.

Abstract

Leigh syndrome (LS) is a common neurodegenerative disease affecting neonates with devastating sequences. One of the characteristic features for LS is the phenotypic polymorphism, which-in part-can be dedicated to variety of genetic causes. A strong correlation with mitochondrial dysfunction has been assumed as the main cause of LS. This was based on the fact that most genetic causes are related to mitochondrial complex I genome. The first animal LS model was designed based on NDUFS4 knockdown. Interestingly, however, this one or others could not recapitulate the whole spectrum of manifestations encountered in different cases of LS. We show in this chapter a new animal model for LS based on silencing of one gene that is reported previously in clinical cases, FOXRED1. The new model carries some differences from previous models in the fact that more histopathological degeneration in dopaminergic system is seen and more behavioral changes can be recognized. FOXRED1 is an interesting gene that is related to complex I assembly, hence, plays important role in different neurodegenerative disorders leading to different clinical manifestations.

Keywords: Animal model; FOXRED1; Gene mutation; Gene silencing; Leigh syndrome; Mitochondrial complex I; Mitochondrial disorders; Neurodegenerative diseases.

MeSH terms

  • Animals
  • Behavior, Animal
  • Disease Models, Animal*
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Immunohistochemistry
  • Leigh Disease / diagnosis
  • Leigh Disease / etiology*
  • Leigh Disease / metabolism
  • Male
  • Mice
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Mutation
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / etiology*
  • Neurodegenerative Diseases / metabolism
  • Symptom Assessment

Substances

  • FOXRED1 protein, human
  • Molecular Chaperones