X-chromosome inactivation (XCI) is an epigenetic process unique to female mammals, and creates a mosaic of cells expressing either the maternal or paternal X-chromosome. Females heterozygous for genes leading to X-linked neurodevelopmental disorders (NDD) exhibit a variety of phenotypes. We hypothesize that variability in the ratio and location of cells expressing the mutant vs wild type (WT) X-chromosome is an underlying cause of phenotypic variability. To investigate this hypothesis, we studied oligodendrocyte (OL) development and myelination in Fragile X syndrome (FXS), a NDD caused by the loss of function of an X-linked gene Fmr1. To probe OLs in the mosaic brain, we developed a novel Cre-loxP based dual-color X-linked cell marking system (ColorX-OL), which enables us to distinguish WT and mutant OLs in FMR1+/- females. Using 2-photon microscopy, single-cell transcriptomics, and in vivo fate-mapping analysis in the cortex of ColorX-OL mice, we found that in FMR1+/- females mutant oligodendrocyte precursor cells (OPCs) differentiated rapidly and prematurely into OLs. A detailed morphometric analysis showed that mutant OLs have complex morphology akin to premyelinating OLs, and form shorter internodes than WT OLs. In contrast, OPCs in mutant males (FMR1y/-) differentiated slower that WT OLs, and exhibit morphology distinct from both mutant and WT OLs in FMR1+/- females. In line with our fate mapping studies, our ongoing analysis confirms distinct transcriptomics profiles between mutant OLs in FXS males and females. Our ongoing analyses suggest that the genetic heterogeneity in the mosaic brain of females induce distinctive pathological changes in WT and mutant OLs.