Supplementary Materials

Supplementary Material for:

MDM2 inhibition rescues neurogenic and cognitive deficits in a mouse model of fragile X syndrome

Yue Li, Michael E. Stockton, Ismat Bhuiyan, Brian E. Eisinger, Yu Gao, Jessica L. Miller, Anita Bhattacharyya, Xinyu Zhao*

*Corresponding author. Email: xinyu.zhao{at}wisc.edu

Published 27 April 2016, Sci. Transl. Med. 8, 336ra61 (2016)
DOI: 10.1126/scitranslmed.aad9370

This PDF file includes:

  • Materials and Methods
  • Fig. S1. FMRP deficiency does not affect dentate gyrus volume but leads to increased number of activated cells in the adult dentate gyrus and increased numbers of GFP+ cells, NSCs, and IPCs in both dorsal and ventral dentate gyrus.
  • Fig. S2. Conditional deletion of FMRP leads to increased NSC numbers in the adult dentate gyrus without affecting the overall dentate gyrus volume.
  • Fig. S3. Adult NPCs derived from Fmr1 KO mice exhibit increased proliferation, reduced neuronal differentiation, but increased astroglial differentiation.
  • Fig. S4. Assessment of optimal protein loading amount for protein quantification using Western blotting.
  • Fig. S5. Quantitative tables for p-MDM2 assessment using Western blot analysis.
  • Fig. S6. Mdm2 mRNA stability analysis in wild-type and Fmr1 KO NPCs.
  • Fig. S7. Fmr1 KO NPCs do not exhibit increased cell death.
  • Fig. S8. Both acute knockdown of MDM2 and treatment with MK-2206 rescue astroglial differentiation of Fmr1 KO NPCs.
  • Fig. S9. Inverse correlation of FMRP and p-MDM2 expression in Fmr1+/−::Nestin-GFP female brains.
  • Fig. S10. Selective deletion of FMRP from Nestin-positive NSCs and their progenies resulted in cognitive deficits, without affecting locomotor activities.
  • Fig. S11. Nutlin-3 treatment does not affect general health and activities of mice.
  • Fig. S12. Increased MDM2/Mdm2 mRNA and p-MDM2 protein expression in the hippocampal and cortical tissues from Fmr1 KO mice and postmortem brains of fragile X syndrome patients.
  • Fig. S13. Models for FMRP regulation of the MDM2 and P53 pathway, which affects adult neurogenesis and cognition.
  • Fig. S14. P53 protein levels did not show significant changes in the hippocampal and cortical tissues from Fmr1 KO mice.
  • Table S2. Neurogenic regulators that regulate adult NSC quiescence and activation.
  • Table S4. Number of physical interactions between FMRP candidate targets identified by PAR-CLIP-seq (table S1) and neurogenic regulators with role in NSC activation obtained from MANGO database and literature search (table S2).
  • References (6581)

[Download PDF]

Other Supplementary Material for this manuscript includes the following:

  • Table S1. FMRP candidate targets (provided as a separate Excel file).
  • Table S3. All known physical interactions with proteins known to be important in NSC activation/proliferation (provided as a separate Excel file).

[Download Tables S1 and S3]