@article{2c41048a90054544a7a6ba1b8bd92193,
title = "Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning",
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.",
author = "Weixiang Guo and Allan, {Andrea M.} and Ruiting Zong and Li Zhang and Johnson, {Eric B.} and Schaller, {Eric G.} and Murthy, {Adeline C.} and Goggin, {Samantha L.} and Eisch, {Amelia J.} and Oostra, {Ben A.} and Nelson, {David L.} and Peng Jin and Xinyu Zhao",
note = "Funding Information: We thank C.T. Strauss for editing the manuscript; H. van Praag, D. Schaffer and T. Xie for critical reading of the manuscript; members of the Zhao lab for discussions; S.J. von HoyningenHuene for technical assistance; D.C. Lagace and R.D. Smrt for technical help; and H. van Praag (US National Institutes of Health (NIH)/National Institute of Aging) and F. Gage (Salk Institute) for the CreGFP construct. This work was supported by grants from the NIH to X.Z. (MH080434 and MH078972) and D.L.N. (HD38038 and HD024064). E.G.S. is supported by an NIH National Institute of Mental Health Career Opportunity for Research training grant (MH19101). Images in this paper were generated in the University of New Mexico Cancer Center Fluorescence Microscopy Shared Resource, funded as detailed here: http://hsc.unm.edu/crtc/microscopy/acknowledgement.shtml/.",
year = "2011",
month = may,
doi = "10.1038/nm.2336",
language = "English (US)",
volume = "17",
pages = "559--565",
journal = "Nature medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "5",
}