Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3

Mona D. Shahbazian, Juan Young, Lisa A. Yuva-Paylor, Corinne M. Spencer, Barbara A. Antalffy, Jeffrey L. Noebels, Dawna L. Armstrong, Richard Paylor, Huda Y. Zoghbi

Research output: Contribution to journalArticle

568 Citations (Scopus)

Abstract

Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), a neurodevelopmental disorder characterized by the loss of language and motor skills during early childhood. We generated mice with a truncating mutation similar to those found in RTT patients. These mice appeared normal and exhibited normal motor function for about 6 weeks, but then developed a progressive neurological disease that includes many features of RTT: tremors, motor impairments, hypoactivity, increased anxiety-related behavior, seizures, kyphosis, and stereotypic forelimb motions. Additionally, we show that although the truncated MeCP2 protein in these mice localizes normally to heterochromatic domains in vivo, histone H3 is hyperacetylated, providing evidence that the chromatin architecture is abnormal and that gene expression may be misregulated in this model of Rett syndrome.

Original languageEnglish
Pages (from-to)243-254
Number of pages12
JournalNeuron
Volume35
Issue number2
DOIs
StatePublished - Jul 18 2002
Externally publishedYes

Fingerprint

Rett Syndrome
Histones
Methyl-CpG-Binding Protein 2
Kyphosis
Mutation
Motor Skills
Forelimb
Tremor
Chromatin
Seizures
Language
Anxiety
Gene Expression
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Shahbazian, M. D., Young, J., Yuva-Paylor, L. A., Spencer, C. M., Antalffy, B. A., Noebels, J. L., ... Zoghbi, H. Y. (2002). Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron, 35(2), 243-254. https://doi.org/10.1016/S0896-6273(02)00768-7

Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. / Shahbazian, Mona D.; Young, Juan; Yuva-Paylor, Lisa A.; Spencer, Corinne M.; Antalffy, Barbara A.; Noebels, Jeffrey L.; Armstrong, Dawna L.; Paylor, Richard; Zoghbi, Huda Y.

In: Neuron, Vol. 35, No. 2, 18.07.2002, p. 243-254.

Research output: Contribution to journalArticle

Shahbazian, MD, Young, J, Yuva-Paylor, LA, Spencer, CM, Antalffy, BA, Noebels, JL, Armstrong, DL, Paylor, R & Zoghbi, HY 2002, 'Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3', Neuron, vol. 35, no. 2, pp. 243-254. https://doi.org/10.1016/S0896-6273(02)00768-7
Shahbazian, Mona D. ; Young, Juan ; Yuva-Paylor, Lisa A. ; Spencer, Corinne M. ; Antalffy, Barbara A. ; Noebels, Jeffrey L. ; Armstrong, Dawna L. ; Paylor, Richard ; Zoghbi, Huda Y. / Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. In: Neuron. 2002 ; Vol. 35, No. 2. pp. 243-254.
@article{9f8fd3ae5247476ca3d1a7cea486c816,
title = "Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3",
abstract = "Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), a neurodevelopmental disorder characterized by the loss of language and motor skills during early childhood. We generated mice with a truncating mutation similar to those found in RTT patients. These mice appeared normal and exhibited normal motor function for about 6 weeks, but then developed a progressive neurological disease that includes many features of RTT: tremors, motor impairments, hypoactivity, increased anxiety-related behavior, seizures, kyphosis, and stereotypic forelimb motions. Additionally, we show that although the truncated MeCP2 protein in these mice localizes normally to heterochromatic domains in vivo, histone H3 is hyperacetylated, providing evidence that the chromatin architecture is abnormal and that gene expression may be misregulated in this model of Rett syndrome.",
author = "Shahbazian, {Mona D.} and Juan Young and Yuva-Paylor, {Lisa A.} and Spencer, {Corinne M.} and Antalffy, {Barbara A.} and Noebels, {Jeffrey L.} and Armstrong, {Dawna L.} and Richard Paylor and Zoghbi, {Huda Y.}",
year = "2002",
month = "7",
day = "18",
doi = "10.1016/S0896-6273(02)00768-7",
language = "English",
volume = "35",
pages = "243--254",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3

AU - Shahbazian, Mona D.

AU - Young, Juan

AU - Yuva-Paylor, Lisa A.

AU - Spencer, Corinne M.

AU - Antalffy, Barbara A.

AU - Noebels, Jeffrey L.

AU - Armstrong, Dawna L.

AU - Paylor, Richard

AU - Zoghbi, Huda Y.

PY - 2002/7/18

Y1 - 2002/7/18

N2 - Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), a neurodevelopmental disorder characterized by the loss of language and motor skills during early childhood. We generated mice with a truncating mutation similar to those found in RTT patients. These mice appeared normal and exhibited normal motor function for about 6 weeks, but then developed a progressive neurological disease that includes many features of RTT: tremors, motor impairments, hypoactivity, increased anxiety-related behavior, seizures, kyphosis, and stereotypic forelimb motions. Additionally, we show that although the truncated MeCP2 protein in these mice localizes normally to heterochromatic domains in vivo, histone H3 is hyperacetylated, providing evidence that the chromatin architecture is abnormal and that gene expression may be misregulated in this model of Rett syndrome.

AB - Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), a neurodevelopmental disorder characterized by the loss of language and motor skills during early childhood. We generated mice with a truncating mutation similar to those found in RTT patients. These mice appeared normal and exhibited normal motor function for about 6 weeks, but then developed a progressive neurological disease that includes many features of RTT: tremors, motor impairments, hypoactivity, increased anxiety-related behavior, seizures, kyphosis, and stereotypic forelimb motions. Additionally, we show that although the truncated MeCP2 protein in these mice localizes normally to heterochromatic domains in vivo, histone H3 is hyperacetylated, providing evidence that the chromatin architecture is abnormal and that gene expression may be misregulated in this model of Rett syndrome.

UR - http://www.scopus.com/inward/record.url?scp=0037130455&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037130455&partnerID=8YFLogxK

U2 - 10.1016/S0896-6273(02)00768-7

DO - 10.1016/S0896-6273(02)00768-7

M3 - Article

VL - 35

SP - 243

EP - 254

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 2

ER -