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 journalArticlepeer-review

188 Scopus citations


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
Issue number5
StatePublished - May 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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