2. Academic Validation
  3. FMR1 mutant marmosets show fragile X syndrome phenotypes

FMR1 mutant marmosets show fragile X syndrome phenotypes

  • Cell Rep. 2025 Sep 23;44(9):116208. doi: 10.1016/j.celrep.2025.116208.
Maria Harbers 1,  Zefeng Wei 1,  Harumi Nakao 1,  Yukiko Abe 1,  Motoki Goto 1,  Moe Tamano 1,  Yusuke Sakai 2,  Kimiko Shimizu 3,  Kazuki Nakao 4,  Yuki Sugaya 5,  Kosuke Itoh 6,  Masanobu Kano 5,  Atsu Aiba 7
Affiliations

Affiliations

  • 1 Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • 2 Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Central Animal Division, National Cancer Center Research Institute, Tokyo, Japan.
  • 3 Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Organization for International Education and Exchange, University of Toyama, Toyama, Japan.
  • 4 Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Institute of Experimental Animal Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • 5 Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • 6 Center for Integrated Human Brain Science, Brain Research Institute, Niigata University, Niigata, Japan.
  • 7 Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: aiba@m.u-tokyo.ac.jp.
PMID: 40912249 DOI: 10.1016/j.celrep.2025.116208
Abstract

Fragile X syndrome (FXS) is the foremost monogenic cause of autism spectrum disorder and intellectual disability, caused by FMR1 gene silencing. Here, we report that common marmosets carrying FMR1 mutation, a non-human primate model for FXS, share common features in behavioral and molecular phenotypes with patients with FXS. Founder mutants with markedly reduced fragile X messenger ribonucleoprotein expression display hyperactivity, spontaneous seizures, and transcriptome changes in synapse-related genes that overlap with those reported in patients with FXS. Although spontaneous seizures in these mutants lead to postnatal lethality, the lethality is rescued by introducing mutations into the GRM5 gene, suggesting that elevated mGluR5 signaling contributes to the phenotype. F1 heterozygous females carrying a uniform mutation exhibit phenotypes associated with FXS, including alterations in vocal development and social preferences, electroencephalographic abnormalities, and impaired motor skills. Thus, female marmosets heterozygous for the FMR1 mutation represent a valuable translational model for investigating FXS mechanisms and potential therapeutic strategies.

Keywords

CP: Neuroscience; fragile X syndrome; mutant marmoset; neurodevelopmental disorders; non-human primate model.

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