Genetic removal of matrix metalloproteinase 9 rescues the symptoms of fragile X syndrome in a mouse model.

ABSTRACT: Fmr1 knock-out (ko) mice display key features of fragile X syndrome (FXS), including delayed dendritic spine maturation and FXS-associated behaviors, such as poor socialization, obsessive-compulsive behavior, and hyperactivity. Here we provide conclusive evidence that matrix metalloproteinase-9 (MMP-9) is necessary to the development of FXS-associated defects in Fmr1 ko mice. Genetic disruption of Mmp-9 rescued key aspects of Fmr1 deficiency, including dendritic spine abnormalities, abnormal mGluR5-dependent LTD, as well as aberrant behaviors in open field and social novelty tests. Remarkably, MMP-9 deficiency also corrected non-neural features of Fmr1 deficiency-specifically macroorchidism-indicating that MMP-9 dysregulation contributes to FXS-associated abnormalities outside the CNS. Fur

SUBMITTER: Sidhu H 

PROVIDER: S-EPMC4107404 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature