Loss of Fmr1 reorganizes the multi-elemental composition of neural and somatic tissues in Fragile X mice

Fragile X Syndrome (FXS) is a leading genetic cause of autism spectrum disorder (ASD) and results from a genetic mutation which silences the expression of Fragile X Messenger Ribonucleoprotein (FMRP). FMRP serves various roles regulating cellular protein synthesis and ion flux. However, a comprehensive comparison of multidimensional elemental balance (i.e., ionome) between FXS genotypes and tissues remains absent from the literature. Here, we measured the multivariate balance of 10 elements (i.e., ionome) in tissues of wild-type and Fmr1-knockout mice to compare ionomic composition of brain and somatic tissues within and across genotypes. We found that homogenized brain tissue including several regions (brain PMHTH; define at first use) differed in elemental balance between genotypes, according to MANOVA. We failed to observe differences between genotypes in the mean ratio of any individual element in PMHTH, but sodium displayed lower variance in knockout than wild-type PMHTH. Knockout striatum displayed lower variance in potassium than wild-type. Knockout olfactory bulbs contained higher mean iron and displayed higher variance in sodium and copper than wild-type. Wild-type feces contained higher mean magnesium and zinc than knockout. These results align with previous work showing FXS pathologies alter electrolytic and metal ion regulation, neuronal excitability, and gastrointestinal function. Further work is needed to identify the source of overall ionomic differences in heterogeneous brain tissue (PMHTH), which could be due to differences among regions. Future work should additionally test how elemental differences relate to function at the cellular level, as well as patterns of individual intake, digestion, assimilation, and/or excretion.