Home > Research > Publications & Outputs > Normal X-inactivation mosaicism in corneas of h...


Text available via DOI:

View graph of relations

Normal X-inactivation mosaicism in corneas of heterozygous FlnaDilp2/+ female mice--a model of human filamin A (FLNA) diseases

Research output: Contribution to journalJournal articlepeer-review

  • Panagiotis Douvaras
  • Weijia Liu
  • Richard L. Mort
  • Lisa McKie
  • Katrine M. West
  • Sally H. Cross
  • Steven D. Morley
  • John D. West
Article number122
<mark>Journal publication date</mark>27/02/2012
<mark>Journal</mark>BMC Research Notes
Number of pages7
Publication StatusPublished
<mark>Original language</mark>English


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. FlnaDilp2/+ 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 FlnaDilp2/+ 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 FlnaDilp2/+ 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 FlnaDilp2/+ and WT X-inactivation mosaics showed similar radial, striped patterns, implying epithelial cell movement was not disrupted in FlnaDilp2/+ 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 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 the mouse FlnaDilp2 mutation on corneal epithelial maintenance or the balance of X-inactivation mosaicism in the corneal epithelium or liver.