Neurobehavioral deficits in the KIKO mouse model of Friedreich's ataxia

Behav Brain Res. 2017 Jan 1;316:183-188. doi: 10.1016/j.bbr.2016.08.053. Epub 2016 Aug 26.


Friedreich's Ataxia (FA) is a pediatric neurodegenerative disease whose clinical presentation includes ataxia, muscle weakness, and peripheral sensory neuropathy. The KIKO mouse is an animal model of FA with frataxin deficiency first described in 2002, but neurobehavioral deficits have never been described in this model. The identification of robust neurobehavioral deficits in KIKO mice could support the testing of drugs for FA, which currently has no approved therapy. We tested 13 neurobehavioral tasks to identify a robust KIKO phenotype: Open Field, Grip Strength Test(s), Cylinder, Skilled Forelimb Grasp Task(s), Treadmill Endurance, Locotronic Motor Coordination, Inverted Screen, Treadscan, and Von Frey. Of these, Inverted Screen, Treadscan and Von Frey produced significant neurobehavioral deficits at >8 months of age, and relate to the clinically relevant endpoints of muscle strength and endurance, gait ataxia, and peripheral insensitivity. Thus we identify robust phenotypic measures related to Friedreich's ataxia clinical endpoints which could be used to test effectiveness of potential drug therapy.

Keywords: Ataxia; Automated gait analysis; Frataxin; Friedreich’s ataxia; Inverted screen; Neurobehavioral; Peripheral sensitivity; Von Frey.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavioral Symptoms / etiology*
  • Disease Models, Animal
  • Exploratory Behavior / physiology
  • Forelimb / physiopathology
  • Friedreich Ataxia / complications*
  • Friedreich Ataxia / genetics*
  • Gait Disorders, Neurologic / etiology*
  • Iron-Binding Proteins / genetics
  • Iron-Binding Proteins / metabolism
  • Locomotion / genetics
  • Mice
  • Mice, Transgenic
  • Muscle Strength / genetics
  • Pain / etiology
  • Pain Measurement
  • Trinucleotide Repeats / genetics


  • Iron-Binding Proteins
  • frataxin