Abstract
Abstract: :
Lymphedema-distichiasis (LD) syndrome (OMIM#153400) is an autosomal dominant disorder characterized by aberrant lashes arising from the meibomian glands (distichiasis) and peripheral lymphedema with pubertal onset. Other less penetrant clinical features include cardiac defects, cleft palate, photophobia, ptosis, and webbed neck. We recently identified FOXC2 as the causative gene of LD. Loss-of function mutations of this gene, which codes for a 501 amino acid forkhead-family transcription factor, have now been described in multiple LD pedigrees. Mice homozygously deficient for Foxc2 die embryonically with heart, vertebral, and cranial defects (Iida et al. 1997) Purpose: To characterize the ocular phenotype of heterozygous Foxc2 knockout mice, which is analogous to the heterozygous genotype of LD patients. Methods: Examination of the anterior segment and eyelids of heterozygote knockout and wild-type mice was performed in a masked fashion in vivo and with histopathology. Results: While penetrance of distichiasis in LD is over 90%, we observed 100% penetrance of distichiasis in heterozygous Foxc2 knockout mice. Histologic examination of the eyelids from heterozygous knockout mice demonstrated aberrant lashes arising from otherwise normal meibomian glands. Conclusions: These mice provide a valuable model for the investigation of the genetics of distichiasis and the normal development of meibomian glands.
Keywords: eyelid • animal model • transcription factors