Background Some abnormalities of mouse corneal epithelial maintenance could be identified

Background Some abnormalities of mouse corneal epithelial maintenance could be identified by the atypical mosaic patterns they produce in X-chromosome inactivation mosaics and chimeras. age-related reduction in stem cell function. Corrected stripe numbers were not reduced in FlnaDilp2/+ compared with WT X-inactivation mosaics and mosaicism was not significantly more unbalanced in the corneal epithelia or livers of FlnaDilp2/+ than wild-type Flna+/+ X-inactivation mosaics. Conclusions Mosaic analysis identified no major effect of buy 1351758-81-0 the mouse FlnaDilp2 mutation on corneal epithelial maintenance or the balance of X-inactivation mosaicism in the corneal epithelium or liver. Background Filamin A is usually a cytoskeleton protein buy 1351758-81-0 with multiple roles that binds to actin and other proteins in many cell types. It is encoded by an X-linked gene, designated FLNA in humans and Flna in mice; mutations in human FLNA cause several types of congenital birth defects [1,2]. Females heterozygous for a loss of function mutation are viable but have periventricular nodular heterotopia (PVNH), a developmental defect in neuronal migration, whereas hemizygous males do not survive. FLNA missense mutations cause four genetic syndromes belonging to the otopalatodigital (OPD) spectrum disorders. The phenotypes of heterozygous females vary according to the syndrome but include skeletal dysplasia, urogenital defects and deafness. Hemizygous males with the more severe syndromes die in utero or shortly after birth but those with the mildest syndrome survive. A mutant Flna mouse with misshapen pupils was recovered from a mutagenesis screen [3]. This new mutant was initially called Dilp2 (dilated pupils 2) but renamed FlnaDilp2 once it was mapped to the Flna locus and the underlying defect identified [4]. The FlnaDilp2 mutation results in nonsense-mediated decay of the Flna mRNA and, therefore, absence of any Flna protein. Heterozygous FlnaDilp2/+ female mice are practical and fertile but possess minor flaws from the eye mainly, sternum and palate whereas FlnaDilp2/Y men perish in utero with center flaws [4]. After X-chromosome inactivation, heterozygous FlnaDilp2/+ and FLNA/+ females are X-inactivation mosaics with two specific cell populations genetically. Even though the FlnaDilp2/+ phenotype continues to be characterised [4], X-inactivation mosaicism had not been investigated. This has been reported to be very unbalanced in some human FLNA/+ females [1,5]. Unbalanced X-inactivation mosaicism may be caused by primary non-random X-chromosome inactivation (e.g. heterozygosity for different Xce alleles in mice [6-11]) or by various secondary selection processes. Some abnormalities of mouse corneal epithelial maintenance can be identified by the abnormal buy 1351758-81-0 mosaic patterns they produce in X-chromosome inactivation mosaics and chimeras. According to the widely accepted, limbal epithelial stem cell (LESC) hypothesis, the corneal epithelium is usually maintained by stem cells located in the limbus between the cornea and conjunctiva [12,13]. These produce daughter transient (or transit) amplifying cells (TACs), which move centripetally in the basal epithelial layer and divide several times before they leave the basal layer and move apically towards the surface from where they are shed. Mosaic patterns in the adult corneal epithelia of wild-type (WT), adult mouse chimeras, X-inactivation mosaics and buy 1351758-81-0 other types of mosaics change from a randomly orientated patchwork to radial stripes between 5 and 8 weeks after TCL1B birth [14-17]. This change in pattern is usually thought to reflect the activation of LESCs at the corneal periphery and the radial stripes are presumed to be formed by lineages of TACs, which buy 1351758-81-0 move centripetally from the limbus towards centre of the cornea. This is consistent with more direct evidence for centripetal movement of corneal epithelial cells [18,19]. The radial striped pattern is disrupted.

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