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.
authors.affiliation: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
authors.forename: Weixiang
authors.initials: W
authors.lastname: Guo
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Allan
authors.forename: Ruiting
authors.initials: R
authors.lastname: Zong
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Eric B
authors.initials: EB
authors.lastname: Johnson
authors.forename: Eric G
authors.initials: EG
authors.lastname: Schaller
authors.forename: Adeline C
authors.initials: AC
authors.lastname: Murthy
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Goggin
authors.forename: Amelia J
authors.initials: AJ
authors.lastname: Eisch
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhao
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000502:physiology*; D005600:Fragile X Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse