Reversal of neurological defects in a mouse model of Rett syndrome

被引:849
作者
Guy, Jacky
Gan, Jian
Selfridge, Jim
Cobb, Stuart
Bird, Adrian
机构
[1] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland
[2] Univ Glasgow, Inst Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland
基金
英国惠康基金;
关键词
D O I
10.1126/science.1138389
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which suggests that this is not a neurodegenerative disorder. An important question for future therapeutic approaches to this and related disorders concerns phenotypic reversibility. Can viable but defective neurons be repaired, or is the damage done during development without normal MeCP2 irrevocable? Using a mouse model, we demonstrate robust phenotypic reversal, as activation of MeCP2 expression leads to striking loss of advanced neurological symptoms in both immature and mature adult animals.
引用
收藏
页码:1143 / 1147
页数:5
相关论文
共 15 条
  • [1] Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2
    Amir, RE
    Van den Veyver, IB
    Wan, M
    Tran, CQ
    Francke, U
    Zoghbi, HY
    [J]. NATURE GENETICS, 1999, 23 (02) : 185 - 188
  • [2] SELECTIVE DENDRITIC ALTERATIONS IN THE CORTEX OF RETT-SYNDROME
    ARMSTRONG, D
    DUNN, JK
    ANTALFFY, B
    TRIVEDI, R
    [J]. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1995, 54 (02) : 195 - 201
  • [3] Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome
    Asaka, Y
    Jugloff, DGM
    Zhang, LA
    Eubanks, JH
    Fitzsimonds, RM
    [J]. NEUROBIOLOGY OF DISEASE, 2006, 21 (01) : 217 - 227
  • [4] Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice
    Chen, RZ
    Akbarian, S
    Tudor, M
    Jaenisch, R
    [J]. NATURE GENETICS, 2001, 27 (03) : 327 - 331
  • [5] Mild overexpression of MeCP2 causes a progressive neurological disorder in mice
    Collins, AL
    Levenson, JM
    Vilaythong, AP
    Richman, R
    Armstrong, DL
    Noebels, JL
    Sweatt, JD
    Zoghbi, HY
    [J]. HUMAN MOLECULAR GENETICS, 2004, 13 (21) : 2679 - 2689
  • [6] A method for the generation of conditional gene repair mutations in mice
    Dragatsis, I
    Zeitlin, S
    [J]. NUCLEIC ACIDS RESEARCH, 2001, 29 (03)
  • [7] A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome
    Guy, J
    Hendrich, B
    Holmes, M
    Martin, JE
    Bird, A
    [J]. NATURE GENETICS, 2001, 27 (03) : 322 - 326
  • [8] Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: A tool for temporally regulated gene activation/inactivation in the mouse
    Hayashi, S
    McMahon, AP
    [J]. DEVELOPMENTAL BIOLOGY, 2002, 244 (02) : 305 - 318
  • [9] MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions
    Kishi, N
    Macklis, JD
    [J]. MOLECULAR AND CELLULAR NEUROSCIENCE, 2004, 27 (03) : 306 - 321
  • [10] DNA methylation and Rett syndrome
    Kriaucionis, S
    Bird, A
    [J]. HUMAN MOLECULAR GENETICS, 2003, 12 : R221 - R227