Preclinical Testing of the Effects of Diet and FMRP on Gut and Brain Barrier Integrity in a Mouse Model of Fragile X
Abstract
The DOD identified a strategical goal for foundational studies to identify mechanisms underlying neurological diseases including fragile X syndrome (FXS) and potential relationships to environmental/neurotoxic exposures. A correlating treatment goal included developing novel therapeutic targets for associated neurological diseases. The DOD also identified a strategic goal for foundational studies to understand correlations between nutrition and disease susceptibility. These DOD needs are juxtaposed in this application, which proposes to determine the effect of fragile X messenger ribonucleoprotein (FMRP) and postnatal diet on gut leakiness in a well-established mouse model of FXS,Fmr1KO mice. Gastrointestinal (GI) problems are a common comorbidity in FXS. There is accumulating evidence suggesting that leaky gut syndrome causes neurological phenotypes. Although ubiquitously expressed, there is a dearth of knowledge regarding the role of FMRP outside of the brain and the mechanism of GI dysfunction in FXS. This DOD Discovery Award proposal seeks to generate novel data on GI barrier function in response to Fmr1 genotype and diet in a mouse model of FXS. The central hypothesis driving this proposal is that FMRP regulates the levels of tight junction proteins in the gut barrier, and the absence of FMRP in FXS leads to leaky gut and neurological sequelae particularly in the context of soy-based diet.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2024
- Accession Number
- AD1228208
Entities
People
- Cara J Westmark
Organizations
- University of Wisconsin–Madison