Fmr1 knockout mouse has a distinctive strain-specific learning impairment

被引:146
作者
Dobkin, C
Rabe, A
Dumas, R
El Idrissi, A
Haubenstock, H
Brown, WT
机构
[1] New York State Inst Basic Res Dev Disabil, Dept Genet, Staten Isl, NY 10314 USA
[2] New York State Inst Basic Res Dev Disabil, Dept Psychobiol, Staten Isl, NY 10314 USA
关键词
fragile X syndrome; mental retardation; cross maze; genetic background; C57BL/6; FVB/N;
D O I
10.1016/S0306-4522(00)00292-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The Fmr1 gene knockout mouse is a model for the human Fragile X mental retardation syndrome. Fmr1 knockout mice with a C57BL/6-129/OlaHsd hybrid background have been reported to have only a very mild deficiency in learning the Morris water maze task. We compared the effect of this knockout mutation on learning in mice with either an FVB/N-129/OlaHsd hybrid background or a C57BL/6 background. When FVB-129 mice were tested in a cross-shaped water maze task, the knockout mice showed a pronounced deficiency in their ability to learn the position of a hidden escape platform in comparison to normal littermates. In contrast, knockout mice with a C57BL/6 background learned the maze just as well as their normal littermates. Fear conditioning did not reveal differences between knockout and normal mice in either background. These results show that silencing the Fmr1 gene clearly interfered with learning a specific visuospatial task in FVB/N-129 hybrid mice but not in C57BL/6 mice. The strain dependence may model the influence of genetic background in the human Fragile X syndrome. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:423 / 429
页数:7
相关论文
共 63 条
  • [1] Expression of FMR1, FXR1, and FXR2 genes in human prenatal tissues
    Agulhon, C
    Blanchet, P
    Kobetz, A
    Marchant, D
    Faucon, N
    Sarda, P
    Moraine, C
    Sittler, A
    Biancalana, V
    Malafosse, A
    Abitbol, M
    [J]. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1999, 58 (08) : 867 - 880
  • [2] HUMAN AND MURINE FMR-1 - ALTERNATIVE SPLICING AND TRANSLATIONAL INITIATION DOWNSTREAM OF THE CGG-REPEAT
    ASHLEY, CT
    SUTCLIFFE, JS
    KUNST, CB
    LEINER, HA
    EICHLER, EE
    NELSON, DL
    WARREN, ST
    [J]. NATURE GENETICS, 1993, 4 (03) : 244 - 251
  • [3] FMR1 PROTEIN - CONSERVED RNP FAMILY DOMAINS AND SELECTIVE RNA-BINDING
    ASHLEY, CT
    WILKINSON, KD
    REINES, D
    WARREN, ST
    [J]. SCIENCE, 1993, 262 (5133) : 563 - 566
  • [4] BAKKER CE, 1994, CELL, V78, P23
  • [5] A novel RNA-binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein
    Bardoni, B
    Schenck, A
    Mandel, JL
    [J]. HUMAN MOLECULAR GENETICS, 1999, 8 (13) : 2557 - 2566
  • [6] BENNETTO MA, 1996, FRAGILE X SYNDROME D
  • [7] LOCALIZATION OF A RETROVIRAL ELEMENT WITHIN THE RD GENE CODING FOR THE BETA-SUBUNIT OF CGMP PHOSPHODIESTERASE
    BOWES, C
    LI, TS
    FRANKEL, WN
    DANCIGER, M
    COFFIN, JM
    APPLEBURY, ML
    FARBER, DB
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (07) : 2955 - 2959
  • [8] BROADHURST PL, 1978, DRUGS INHERITANCE BE
  • [9] Purified recombinant Fmrp exhibits selective RNA binding as an intrinsic property of the fragile X mental retardation protein
    Brown, V
    Small, K
    Lakkis, L
    Feng, Y
    Gunter, C
    Wilkinson, KD
    Warren, ST
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (25) : 15521 - 15527
  • [10] Quantitative trait loci analysis affecting contextual conditioning in mice
    Caldarone, B
    Saavedra, C
    Tartaglia, K
    Wehner, JM
    Dudek, BC
    Flaherty, L
    [J]. NATURE GENETICS, 1997, 17 (03) : 335 - 337