title: Normal X-inactivation mosaicism in corneas of heterozygous FlnaDilp2/+ female mice--a model of human filamin A (FLNA) diseases.
abstract: 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.
authors.affiliation: Division of Reproductive and Developmental Sciences, Genes and Development Group, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Douvaras
authors.forename: Weijia
authors.initials: W
authors.lastname: Liu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Mort
authors.forename: Lisa
authors.initials: L
authors.lastname: McKie
authors.forename: Katrine M
authors.initials: KM
authors.lastname: West
authors.forename: Sally H
authors.initials: SH
authors.lastname: Cross
authors.forename: Steven D
authors.initials: SD
authors.lastname: Morley
authors.forename: John D
authors.initials: JD
authors.lastname: West
mesh_terms: D000367:Age Factors; D000818:Animals; D002465:Cell Movement; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D064448:Filamins; D050172:Genes, X-Linked; D005838:Genotype; D006579:Heterozygote; D006651:Histocytochemistry; D006801:Humans; D007763:Lac Operon; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009030:Mosaicism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019076:Transgenes; D049951:X Chromosome Inactivation; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D005136:Eye Proteins; D064448:Filamins; C529499:FlnA protein, mouse; D009419:Nerve Tissue Proteins; D001616:beta-Galactosidase