Impaired sensorimotor gating in Fmr1 knock out and Fragile X premutation model mice.
Behav Brain Res
; 267: 42-5, 2014 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-24657592
ABSTRACT
Fragile X syndrome (FXS) is a common inherited cause of intellectual disability that results from a CGG repeat expansion in the FMR1 gene. Large repeat expansions trigger both transcriptional and translational suppression of Fragile X protein (FMRP) production. Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is an allelic neurodegenerative disease caused by smaller "pre-mutation" CGG repeat expansions that enhance FMR1 transcription but lead to translational inefficiency and reduced FMRP expression in animal models. Sensorimotor gating as measured by pre-pulse inhibition (PPI) is altered in both FXS patients and Fmr1 knock out (KO) mice. Similarly, FXTAS patients have demonstrated PPI deficits. Recent work suggests there may be overlapping synaptic defects between Fmr1 KO and CGG knock-in premutation mouse models (CGG KI). We therefore sought to interrogate PPI in CGG KI mice. Using a quiet PPI protocol more akin to human testing conditions, we find that Fmr1 KO animals have significantly impaired PPI. Using this same protocol, we find CGG KI mice demonstrate an age-dependent impairment in PPI compared to wild type (WT) controls. This study describes a novel phenotype in CGG KI mice that can be used in future therapeutic development targeting premutation associated symptoms.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil
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Filtrado Sensorial
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Inhibición Prepulso
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Síndrome del Cromosoma X Frágil
Tipo de estudio:
Guideline
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Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Behav Brain Res
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos