Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning

Weixiang Guo, Andrea M. Allan, Ruiting Zong, Li Zhang, Eric B. Johnson, Eric G. Schaller, Adeline C. Murthy, Samantha L. Goggin, Amelia J. Eisch, Ben A. Oostra, David L. Nelson, Peng Jin, Xinyu Zhao

Research output: Contribution to journalArticle

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Abstract

Deficiency in fragile X mental retardation protein (FMRP) results in fragile X syndrome (FXS), an inherited form of intellectual disability. Despite extensive research, it is unclear how FMRP deficiency contributes to the cognitive deficits in FXS. Fmrp-null mice show reduced adult hippocampal neurogenesis. As Fmrp is also enriched in mature neurons, we investigated the function of Fmrp expression in neural stem and progenitor cells (aNSCs) and its role in adult neurogenesis. Here we show that ablation of Fmrp in aNSCs by inducible gene recombination leads to reduced hippocampal neurogenesis in vitro and in vivo, as well as markedly impairing hippocampus-dependent learning in mice. Conversely, restoration of Fmrp expression specifically in aNSCs rescues these learning deficits in Fmrp-deficient mice. These data suggest that defective adult neurogenesis may contribute to the learning impairment seen in FXS, and these learning deficits can be rectified by delayed restoration of Fmrp specifically in aNSCs.

Original languageEnglish (US)
Pages (from-to)559-565
Number of pages7
JournalNature Medicine
Volume17
Issue number5
DOIs
StatePublished - May 2011

Fingerprint

Fragile X Mental Retardation Protein
Adult Stem Cells
Neural Stem Cells
Neurogenesis
Ablation
Stem cells
Fragile X Syndrome
Restoration
Hippocampus
Learning
Neurons
Genes
Protein Deficiency
Intellectual Disability
Genetic Recombination
Stem Cells
Research

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Guo, W., Allan, A. M., Zong, R., Zhang, L., Johnson, E. B., Schaller, E. G., ... Zhao, X. (2011). Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. Nature Medicine, 17(5), 559-565. https://doi.org/10.1038/nm.2336

Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. / Guo, Weixiang; Allan, Andrea M.; Zong, Ruiting; Zhang, Li; Johnson, Eric B.; Schaller, Eric G.; Murthy, Adeline C.; Goggin, Samantha L.; Eisch, Amelia J.; Oostra, Ben A.; Nelson, David L.; Jin, Peng; Zhao, Xinyu.

In: Nature Medicine, Vol. 17, No. 5, 05.2011, p. 559-565.

Research output: Contribution to journalArticle

Guo, W, Allan, AM, Zong, R, Zhang, L, Johnson, EB, Schaller, EG, Murthy, AC, Goggin, SL, Eisch, AJ, Oostra, BA, Nelson, DL, Jin, P & Zhao, X 2011, 'Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning', Nature Medicine, vol. 17, no. 5, pp. 559-565. https://doi.org/10.1038/nm.2336
Guo W, Allan AM, Zong R, Zhang L, Johnson EB, Schaller EG et al. Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. Nature Medicine. 2011 May;17(5):559-565. https://doi.org/10.1038/nm.2336
Guo, Weixiang ; Allan, Andrea M. ; Zong, Ruiting ; Zhang, Li ; Johnson, Eric B. ; Schaller, Eric G. ; Murthy, Adeline C. ; Goggin, Samantha L. ; Eisch, Amelia J. ; Oostra, Ben A. ; Nelson, David L. ; Jin, Peng ; Zhao, Xinyu. / Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. In: Nature Medicine. 2011 ; Vol. 17, No. 5. pp. 559-565.
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