# Soy Protein Isolate Affects Blood and Brain Biomarker Expression in a Mouse Model of Fragile X

## TL;DR

This study shows that soy protein in diets affects blood and brain protein levels in mice with a genetic disorder called Fragile X, highlighting the importance of diet in influencing biomarkers.

## Contribution

The study identifies diet-induced changes in protein biomarkers in a mouse model of Fragile X syndrome, emphasizing gene-diet interactions.

## Key findings

- Prolactin levels in blood plasma were significantly elevated in Fmr1KO female mice with the AIN-93G/casein diet.
- GDF-9 was the only protein differentially expressed between WT and Fmr1KO male mice fed AIN-93G/soy.
- IGFBP5 was the only protein differentially expressed as a function of soy in a pelleted infant formula study.

## Abstract

Fragile X syndrome is characterized by the diminished expression of the fragile X messenger ribonucleoprotein (FMRP), a ubiquitously expressed RNA binding protein with numerous functions in cells. Our prior work found significant differences in physiological and behavioral outcomes as a function of FMRP levels and in response to diet in mice. Here, we assess protein biomarker levels as a function of FMRP levels, sex and matched casein and soy protein isolate-based purified ingredient diets in Fmr1KO and littermate mice. Brain regions (cortex, hippocampus, and hypothalamus) and blood plasma were analyzed by RayBiotech’s Quantibody® Mouse Cytokine Antibody Array 640 to quantitate the expression of 640 proteins. The main findings were the identification of numerous proteins that were differentially expressed in response to diet, sex and/or genotype. Of note, prolactin (PRL) levels in blood plasma were significantly elevated in Fmr1KO female mice as a function of genotype and sex selectively with the AIN-93G/casein diet. Also, using a moderately stringent significance cutoff, growth differentiation factor 9 (GDF-9) in plasma from mice fed AIN-93G/soy was the only protein studied by Quantibody arrays that was differentially expressed between WT and Fmr1KO male mice. When comparing the results from a pelleted infant formula study with AIN-93G-based diets, insulin-like growth factor binding protein 5 (IGFBP5) in plasma was the only protein differentially expressed as a function of soy in the diet. There was no overlap in statistically significant results when comparing tissue analyzed by mass spectrometry versus Quantibody arrays from mice maintained on AIN-93G-based diets. In conclusion, gene–diet interactions affect protein expression in Fmr1KO and littermate mice and need to be considered in study design.