Expression of FMR1, FXR1, and FXR2 genes in human prenatal tissues

We analyzed the distribution of FMR1, FXR1, FXR2 mRNA, and FMRP in whole no rmal human embryos and in the brains of normal and fragile X fetuses. The d istributions of mRNA for the 3 genes in normal whole embryos and in the bra ins of normal male and female carrier fetuses were similar, with large amou nts of mRNA in the nervous system and in several non-nervous system tissues . No FMR1 (mRNA and protein) was detected and no evident neuropathologic ab normalities found in the brains of male carrier fetuses, suggesting that th e FMR1 product (FMRP) may have no crucial function in early stages of nervo us system development. FXR1 and FXR2 mRNA had the same distribution and sim ilar intensity in the brains of normal and pathologic fetuses (female and m ale carriers). The coexpression in the same tissues of FMR1, FXR1, and FXR2 , associated with the normal expression of FXR1 and FXR2 and the absence of obvious neuropathological abnormalities in pathological brains, supports t he notion that the FXR1 and FXR2 proteins partially compensate for FMRP fun ction. However, the absence of significant overexpression of FXR1 and FXR2 in pathological brains suggests that these genes do not compensate for the lack of FMR1 expression. Alternatively, FMR1, FXR1, and FXR2 proteins may n ot have compensatory functions, but instead may regulate functions by heter o or homo oligomerization, as suggested by other studies. Thus, a dominant negative effect of abnormal multimeric protein complexes lacking FMRP (e.g. by modification of FXR1 and FXR2 protein functions) may result in the frag ile X syndrome phenotype.