Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice

Molly Foote, Gloria Arque, Robert F Berman, Mónica Santos

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55–200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments.

Original languageEnglish (US)
Pages (from-to)611-622
Number of pages12
JournalCerebellum
Volume15
Issue number5
DOIs
StatePublished - Oct 1 2016

Fingerprint

Fragile X Mental Retardation Protein
Gait Ataxia
Neurobiology
Tremor
Reproducibility of Results
Neurodegenerative Diseases
Dementia
Animal Models
Messenger RNA
Fragile X Tremor Ataxia Syndrome
Genes
Late Onset Disorders

Keywords

  • CGG trinucleotide repeat
  • Fragile X mental retardation (FMR1) gene
  • Fragile X premutation
  • Fragile X-associated tremor/ataxia syndrome (FXTAS)
  • Mouse models
  • Neurodegenerative disorder

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice. / Foote, Molly; Arque, Gloria; Berman, Robert F; Santos, Mónica.

In: Cerebellum, Vol. 15, No. 5, 01.10.2016, p. 611-622.

Research output: Contribution to journalReview article

Foote, Molly ; Arque, Gloria ; Berman, Robert F ; Santos, Mónica. / Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice. In: Cerebellum. 2016 ; Vol. 15, No. 5. pp. 611-622.
@article{2bab34be69bd4183a86bed6585b809e0,
title = "Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice",
abstract = "Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55–200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments.",
keywords = "CGG trinucleotide repeat, Fragile X mental retardation (FMR1) gene, Fragile X premutation, Fragile X-associated tremor/ataxia syndrome (FXTAS), Mouse models, Neurodegenerative disorder",
author = "Molly Foote and Gloria Arque and Berman, {Robert F} and M{\'o}nica Santos",
year = "2016",
month = "10",
day = "1",
doi = "10.1007/s12311-016-0797-6",
language = "English (US)",
volume = "15",
pages = "611--622",
journal = "Cerebellum",
issn = "1473-4222",
publisher = "Springer New York",
number = "5",

}

TY - JOUR

T1 - Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice

AU - Foote, Molly

AU - Arque, Gloria

AU - Berman, Robert F

AU - Santos, Mónica

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55–200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments.

AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55–200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments.

KW - CGG trinucleotide repeat

KW - Fragile X mental retardation (FMR1) gene

KW - Fragile X premutation

KW - Fragile X-associated tremor/ataxia syndrome (FXTAS)

KW - Mouse models

KW - Neurodegenerative disorder

UR - http://www.scopus.com/inward/record.url?scp=84986327481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84986327481&partnerID=8YFLogxK

U2 - 10.1007/s12311-016-0797-6

DO - 10.1007/s12311-016-0797-6

M3 - Review article

VL - 15

SP - 611

EP - 622

JO - Cerebellum

JF - Cerebellum

SN - 1473-4222

IS - 5

ER -