Neuropeptide Release is Impaired in a Mouse Model of Fragile X Mental Retardation Syndrome.
Fragile X syndrome (FXS), an inherited disorder characterized by mental retardation and autismlike behaviors, is caused by the failure to transcribe the gene for fragile X mental retardation protein (FMRP), a translational regulator and transporter of select mRNAs. FXS model mice (Fmr1 KO mice) exhibit impaired neuropeptide release. Release of biogenic amines does not differ between wild-type (WT) and Fmr1 KO mice. Rab3A, an mRNA cargo of FMRP involved in the recruitment of vesicles, is decreased by ∼50% in synaptoneurosomes of Fmr1 KO mice; however, the number of dense-core vesicles (DCVs) does not differ between WT and Fmr1 KO mice. Therefore, deficits associated with FXS may reflect this aberrant vesicle release, specifically involving docking and fusion of peptidergic DCVs, and may lead to defective maturation/maintenance of synaptic connections.
Annangudi
Suresh P
SP
Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Luszpak
Agatha E
AE
Kim
Soong Ho
SH
Ren
Shifang
S
Hatcher
Nathan G
NG
Weiler
Ivan Jeanne
IJ
Thornley
Keith T
KT
Kile
Brian M
BM
Wightman
R Mark
RM
Greenough
William T
WT
Sweedler
Jonathan V
JV