Peroxidasin is essential for eye development in the mouse

Xiaohe Yan, Sibylle Sabrautzki, Marion Horsch, Helmut Fuchs, Valerie Gailus-Durner, Johannes Beckers, Martin Hrabě de Angelis, Jochen Graw

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Mutations in Peroxidasin (PXDN) cause severe inherited eye disorders in humans, such as congenital cataract, corneal opacity and developmental glaucoma. The role of peroxidasin during eye development is poorly understood. Here,wedescribethe firstPxdnmousemutant whichwasinducedbyENU(N-ethyl-N-nitrosourea)andled to a recessive phenotype. Sequence analysis of cDNArevealed a T3816Amutation resulting in a premature stop codon (Cys1272X) in the peroxidase domain. This mutation causes severe anterior segment dysgenesis and microphthalmia resembling the manifestations in patients with PXDN mutations. The proliferation and differentiation of the lens is disrupted in association with aberrant expression of transcription factor genes (Pax6 and Foxe3) in mutant eyes. Additionally, Pxdn is involved in the consolidation of the basement membrane and lens epithelium adhesion in the ocular lens. Lens material including g-crystallin is extruded into the anterior and posterior chamber due to local loss of structural integrity of the lens capsule as a secondary damage to the anteriorsegmentdevelopmentleadingtocongenital ocularinflammation. Moreover,Pxdnmutantsexhibited an early-onset glaucoma and progressive retinal dysgenesis. Transcriptome profiling revealed that peroxidasin affects the transcription of developmental and eye disease-related genes at early eye development. These findings suggest that peroxidasin is necessary for cell proliferation and differentiation and for basement membrane consolidation during eye development. Our studies provide pathogenic mechanisms of PXDN mutationinduced congenital eye diseases.

Original languageEnglish
Pages (from-to)5597-5614
Number of pages18
JournalHuman Molecular Genetics
Issue number21
StatePublished - 1 Nov 2014


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