biostudies-literatureUnknown9(1)Hosoi YX-chromosome inactivation (XCI) is an essential epigenetic process in female mammalian development. Although cell-based studies suggest the potential importance of the Ftx long non-protein-coding RNA (lncRNA) in XCI, its physiological roles in vivo remain unclear. Here we show that targeted deletion of X-linked mouse Ftx lncRNA causes eye abnormalities resembling human microphthalmia in a subset of females but rarely in males. This inheritance pattern cannot be explained by X-linked dominant or recessive inheritance, where males typically show a more severe phenotype than females. In Ftx-deficient mice, some X-linked genes remain active on the inactive X, suggesting that defects in random XCI in somatic cells cause a substantially female-specific phenotype. The expression level of Xist, a Nature communications3829https://www.ebi.ac.uk/biostudies/studies/S-EPMC6148026biostudies-literatureFemale mice lacking Ftx lncRNA exhibit impaired X-chromosome inactivation and a microphthalmia-like phenotype.PMC6148026Kohda TShiura HSado TKobayashi SIshino FHasuwa HHosoi YSoma MAbe KfalseFemale mice lacking Ftx lncRNA exhibit impaired X-chromosome inactivation and a microphthalmia-like phenotype.X-chromosome inactivation (XCI) is an essential epigenetic process in female mammalian development. Although cell-based studies suggest the potential importance of the Ftx long non-protein-coding RNA (lncRNA) in XCI, its physiological roles in vivo remain unclear. Here we show that targeted deletion of X-linked mouse Ftx lncRNA causes eye abnormalities resembling human microphthalmia in a subset of females but rarely in males. This inheritance pattern cannot be explained by X-linked dominant or recessive inheritance, where males typically show a more severe phenotype than females. In Ftx-deficient mice, some X-linked genes remain active on the inactive X, suggesting that defects in random XCI in somatic cells cause a substantially female-specific phenotype. The expression level of Xist, a 2018-01-01T00:00:00Z2018 Sep2026-05-01T18:24:00.952Z2019-03-27T00:05:08ZS-EPMC61480263023740210.1038/s41467-018-06327-6