Boeck Brynne, Mao Yingqing, Huang Ruo-Pan, Westmark Cara J
Department of Neurology, University of Wisconsin, Madison, WI 53706, USA.
RayBiotech, Inc., Peachtree Corners, GA 30092, USA.
Int J Mol Sci. 2025 Jun 26;26(13):6137. doi: 10.3390/ijms26136137.
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 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 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 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 and littermate mice and need to be considered in study design.
脆性X综合征的特征是脆性X信使核糖核蛋白（FMRP）表达减少，FMRP是一种在细胞中广泛表达且具有多种功能的RNA结合蛋白。我们之前的研究发现，在小鼠中，生理和行为结果因FMRP水平以及对饮食的反应不同而存在显著差异。在此，我们评估了同窝小鼠中蛋白质生物标志物水平与FMRP水平、性别以及匹配的基于酪蛋白和大豆分离蛋白的纯化成分饮食之间的关系。通过RayBiotech的定量抗体小鼠细胞因子抗体阵列640对脑区（皮层、海马体和下丘脑）和血浆进行分析，以定量640种蛋白质的表达。主要发现是鉴定出了许多因饮食、性别和/或基因型而差异表达的蛋白质。值得注意的是，在采用AIN-93G/酪蛋白饮食时，雌性小鼠血浆中的催乳素（PRL）水平因基因型和性别而显著升高。此外，使用适度严格的显著性临界值，喂食AIN-93G/大豆的小鼠血浆中的生长分化因子9（GDF-9）是定量抗体阵列研究的唯一一种在野生型和脆性X综合征雄性小鼠之间差异表达的蛋白质。当将基于AIN-93G饮食的颗粒状婴儿配方奶粉研究结果进行比较时，血浆中的胰岛素样生长因子结合蛋白5（IGFBP5）是唯一一种因饮食中的大豆成分而差异表达的蛋白质。在比较基于AIN-93G饮食的小鼠经质谱分析的组织与定量抗体阵列的结果时，统计学上显著的结果没有重叠。总之，基因-饮食相互作用会影响脆性X综合征小鼠和同窝小鼠的蛋白质表达，在研究设计中需要加以考虑。
