Mouse Models of the Fragile X Tremor/Ataxia Syndrome (FXTAS) and the Fragile X Premutation

Robert F Berman, Jared J. Schwartzer, Michael Ryan Hunsaker

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-developing neurodegenerative disease that develops in some carriers of the fragile X premutation (PM) as the result of a 55-200 CGG trinucleotide repeat expansion in fragile X mental retardation 1 gene (FMR1). CGG-repeat knockin mouse models have been developed that model much, but not all, of the molecular, histological, and neurobehavioral pathology seen in FXTAS and in some affected PM carriers. This includes elevated Fmr1 mRNA, reduced levels of fragile X mental retardation protein (FMRP), intranuclear inclusions in neurons and astrocytes, mild motor dysfunction resembling ataxia, anxiety, and cognitive impairments. These mice have provided insight into when disease processes become evident during development, the molecular mechanisms of pathology, and the scope of neurobehavioral involvement. Moreover, these mice are being used pre-clinically to develop and test possible treatment approaches that may improve neurological function in affected individuals. This chapter describes the features of FXTAS, recently recognized pathology in some affected PM carriers, and the development and use of mouse models to study these disorders.

Original languageEnglish (US)
Title of host publicationMovement Disorders: Genetics and Models: Second Edition
PublisherElsevier Inc.
Pages641-652
Number of pages12
ISBN (Print)9780124051959
DOIs
StatePublished - Oct 29 2014

Fingerprint

Fragile X Mental Retardation Protein
Trinucleotide Repeat Expansion
Pathology
Intranuclear Inclusion Bodies
Molecular Pathology
Ataxia
Astrocytes
Intellectual Disability
Neurodegenerative Diseases
Anxiety
Neurons
Messenger RNA
Fragile X Tremor Ataxia Syndrome
Genes
Cognitive Dysfunction

Keywords

  • Ataxia
  • CGG repeat expansion
  • FMR1
  • FMRP
  • Fragile X premutation
  • FXTAS
  • Mouse models
  • Tremor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Berman, R. F., Schwartzer, J. J., & Hunsaker, M. R. (2014). Mouse Models of the Fragile X Tremor/Ataxia Syndrome (FXTAS) and the Fragile X Premutation. In Movement Disorders: Genetics and Models: Second Edition (pp. 641-652). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-405195-9.00039-1

Mouse Models of the Fragile X Tremor/Ataxia Syndrome (FXTAS) and the Fragile X Premutation. / Berman, Robert F; Schwartzer, Jared J.; Hunsaker, Michael Ryan.

Movement Disorders: Genetics and Models: Second Edition. Elsevier Inc., 2014. p. 641-652.

Research output: Chapter in Book/Report/Conference proceedingChapter

Berman, RF, Schwartzer, JJ & Hunsaker, MR 2014, Mouse Models of the Fragile X Tremor/Ataxia Syndrome (FXTAS) and the Fragile X Premutation. in Movement Disorders: Genetics and Models: Second Edition. Elsevier Inc., pp. 641-652. https://doi.org/10.1016/B978-0-12-405195-9.00039-1
Berman RF, Schwartzer JJ, Hunsaker MR. Mouse Models of the Fragile X Tremor/Ataxia Syndrome (FXTAS) and the Fragile X Premutation. In Movement Disorders: Genetics and Models: Second Edition. Elsevier Inc. 2014. p. 641-652 https://doi.org/10.1016/B978-0-12-405195-9.00039-1
Berman, Robert F ; Schwartzer, Jared J. ; Hunsaker, Michael Ryan. / Mouse Models of the Fragile X Tremor/Ataxia Syndrome (FXTAS) and the Fragile X Premutation. Movement Disorders: Genetics and Models: Second Edition. Elsevier Inc., 2014. pp. 641-652
@inbook{b359e6b973f3471baade8fe2af36eb86,
title = "Mouse Models of the Fragile X Tremor/Ataxia Syndrome (FXTAS) and the Fragile X Premutation",
abstract = "Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-developing neurodegenerative disease that develops in some carriers of the fragile X premutation (PM) as the result of a 55-200 CGG trinucleotide repeat expansion in fragile X mental retardation 1 gene (FMR1). CGG-repeat knockin mouse models have been developed that model much, but not all, of the molecular, histological, and neurobehavioral pathology seen in FXTAS and in some affected PM carriers. This includes elevated Fmr1 mRNA, reduced levels of fragile X mental retardation protein (FMRP), intranuclear inclusions in neurons and astrocytes, mild motor dysfunction resembling ataxia, anxiety, and cognitive impairments. These mice have provided insight into when disease processes become evident during development, the molecular mechanisms of pathology, and the scope of neurobehavioral involvement. Moreover, these mice are being used pre-clinically to develop and test possible treatment approaches that may improve neurological function in affected individuals. This chapter describes the features of FXTAS, recently recognized pathology in some affected PM carriers, and the development and use of mouse models to study these disorders.",
keywords = "Ataxia, CGG repeat expansion, FMR1, FMRP, Fragile X premutation, FXTAS, Mouse models, Tremor",
author = "Berman, {Robert F} and Schwartzer, {Jared J.} and Hunsaker, {Michael Ryan}",
year = "2014",
month = "10",
day = "29",
doi = "10.1016/B978-0-12-405195-9.00039-1",
language = "English (US)",
isbn = "9780124051959",
pages = "641--652",
booktitle = "Movement Disorders: Genetics and Models: Second Edition",
publisher = "Elsevier Inc.",

}

TY - CHAP

T1 - Mouse Models of the Fragile X Tremor/Ataxia Syndrome (FXTAS) and the Fragile X Premutation

AU - Berman, Robert F

AU - Schwartzer, Jared J.

AU - Hunsaker, Michael Ryan

PY - 2014/10/29

Y1 - 2014/10/29

N2 - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-developing neurodegenerative disease that develops in some carriers of the fragile X premutation (PM) as the result of a 55-200 CGG trinucleotide repeat expansion in fragile X mental retardation 1 gene (FMR1). CGG-repeat knockin mouse models have been developed that model much, but not all, of the molecular, histological, and neurobehavioral pathology seen in FXTAS and in some affected PM carriers. This includes elevated Fmr1 mRNA, reduced levels of fragile X mental retardation protein (FMRP), intranuclear inclusions in neurons and astrocytes, mild motor dysfunction resembling ataxia, anxiety, and cognitive impairments. These mice have provided insight into when disease processes become evident during development, the molecular mechanisms of pathology, and the scope of neurobehavioral involvement. Moreover, these mice are being used pre-clinically to develop and test possible treatment approaches that may improve neurological function in affected individuals. This chapter describes the features of FXTAS, recently recognized pathology in some affected PM carriers, and the development and use of mouse models to study these disorders.

AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-developing neurodegenerative disease that develops in some carriers of the fragile X premutation (PM) as the result of a 55-200 CGG trinucleotide repeat expansion in fragile X mental retardation 1 gene (FMR1). CGG-repeat knockin mouse models have been developed that model much, but not all, of the molecular, histological, and neurobehavioral pathology seen in FXTAS and in some affected PM carriers. This includes elevated Fmr1 mRNA, reduced levels of fragile X mental retardation protein (FMRP), intranuclear inclusions in neurons and astrocytes, mild motor dysfunction resembling ataxia, anxiety, and cognitive impairments. These mice have provided insight into when disease processes become evident during development, the molecular mechanisms of pathology, and the scope of neurobehavioral involvement. Moreover, these mice are being used pre-clinically to develop and test possible treatment approaches that may improve neurological function in affected individuals. This chapter describes the features of FXTAS, recently recognized pathology in some affected PM carriers, and the development and use of mouse models to study these disorders.

KW - Ataxia

KW - CGG repeat expansion

KW - FMR1

KW - FMRP

KW - Fragile X premutation

KW - FXTAS

KW - Mouse models

KW - Tremor

UR - http://www.scopus.com/inward/record.url?scp=84943236359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84943236359&partnerID=8YFLogxK

U2 - 10.1016/B978-0-12-405195-9.00039-1

DO - 10.1016/B978-0-12-405195-9.00039-1

M3 - Chapter

AN - SCOPUS:84943236359

SN - 9780124051959

SP - 641

EP - 652

BT - Movement Disorders: Genetics and Models: Second Edition

PB - Elsevier Inc.

ER -