Normal X-inactivation mosaicism in corneas of heterozygous Flna(Dilp2/+ )female mice--a model of human Filamin A (FLNA) diseases

BACKGROUND: Some abnormalities of mouse corneal epithelial maintenance can be identified by the atypical mosaic patterns they produce in X-chromosome inactivation mosaics and chimeras. Human FLNA/+ females, heterozygous for X-linked, filamin A gene (FLNA) mutations, display a range of disorders and X-inactivation mosaicism is sometimes quantitatively unbalanced. Flna(Dilp2/+ )mice, heterozygous for an X-linked filamin A (Flna) nonsense mutation have variable eye, skeletal and other abnormalities, but X-inactivation mosaicism has not been investigated. The aim of this study was to determine whether X-inactivation mosaicism in the corneal epithelia of Flna(Dilp2/+ )mice was affected in any way that might predict abnormal corneal epithelial maintenance. RESULTS: X-chromosome inactivation mosaicism was studied in the corneal epithelium and a control tissue (liver) of Flna(Dilp2/+ )and wild-type (WT) female X-inactivation mosaics, hemizygous for the X-linked, LacZ reporter H253 transgene, using β-galactosidase histochemical staining. The corneal epithelia of Flna(Dilp2/+ )and WT X-inactivation mosaics showed similar radial, striped patterns, implying epithelial cell movement was not disrupted in Flna(Dilp2/+ )corneas. Corrected stripe numbers declined with age overall (but not significantly for either genotype individually), consistent with previous reports suggesting an age-related reduction in stem cell function. Corrected stripe numbers were not reduced in Flna(Dilp2/+ )compared with WT X-inactivation mosaics and mosaicism was not significantly more unbalanced in the corneal epithelia or livers of Flna(Dilp2/+ )than wild-type Flna(+/+ )X-inactivation mosaics. CONCLUSIONS: Mosaic analysis identified no major effect of the mouse Flna(Dilp2 )mutation on corneal epithelial maintenance or the balance of X-inactivation mosaicism in the corneal epithelium or liver.