Motor, Somatosensory, Viscerosensory and Metabolic Impairments in a Heterozygous Female Rat Model of Rett Syndrome

Int J Mol Sci. 2017 Dec 29;19(1):97. doi: 10.3390/ijms19010097.


Rett Syndrome (RTT), an autism-related disorder caused by mutation of the X-linked Methyl CpG-binding Protein 2 (MECP2) gene, is characterized by severe cognitive and intellectual deficits. While cognitive deficits are well-documented in humans and rodent models, impairments of sensory, motor and metabolic functions also occur but remain poorly understood. To better understand non-cognitive deficits in RTT, we studied female rats heterozygous for Mecp2 mutation (Mecp2-/x); unlike commonly used male Mecp2-/y rodent models, this more closely approximates human RTT where males rarely survive. Mecp2-/x rats showed rapid, progressive decline of motor coordination through six months of age as assessed by rotarod performance, accompanied by deficits in gait and posture. Mecp2-/x rats were hyper-responsive to noxious pressure and cold, but showed visceral hyposensitivity when tested by colorectal distension. Mecp2-/x rats ate less, drank more, and had more body fat resulting in increased weight gain. Our findings reveal an array of progressive non-cognitive deficits in this rat model that are likely to contribute to the compromised quality of life that characterizes RTT.

Keywords: autism spectrum disorder; behavior; feeding.

MeSH terms

  • Animals
  • Ataxia / genetics*
  • Ataxia / metabolism
  • Ataxia / physiopathology
  • Disease Models, Animal
  • Eating
  • Female
  • Gait
  • Heterozygote
  • Humans
  • Methyl-CpG-Binding Protein 2 / deficiency
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Mutation*
  • Posture
  • Psychomotor Disorders / genetics*
  • Psychomotor Disorders / metabolism
  • Psychomotor Disorders / physiopathology
  • Rats
  • Rats, Transgenic
  • Rett Syndrome / genetics*
  • Rett Syndrome / metabolism
  • Rett Syndrome / physiopathology
  • Rotarod Performance Test


  • Mecp2 protein, rat
  • Methyl-CpG-Binding Protein 2