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Int J Mol Sci. 2017 Dec 29;19(1). pii: E97. doi: 10.3390/ijms19010097.

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

Author information

1
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Aritra.Bhattacherjee@childrens.harvard.edu.
2
Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. Aritra.Bhattacherjee@childrens.harvard.edu.
3
Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. mwinter2@kumc.edu.
4
Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. leggimann@kumc.edu.
5
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. mu2@uthsc.edu.
6
Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. mu2@uthsc.edu.
7
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. sgunewardena@kumc.edu.
8
Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. sgunewardena@kumc.edu.
9
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. zliao@kumc.edu.
10
Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. zliao@kumc.edu.
11
Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. jchristianson@kumc.edu.
12
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. jchristianson@kumc.edu.
13
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. psmith@kumc.edu.
14
Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. psmith@kumc.edu.

Abstract

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

PMID:
29286317
PMCID:
PMC5796047
DOI:
10.3390/ijms19010097
[Indexed for MEDLINE]
Free PMC Article

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