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Xiaohe Yan, Jiantao Wang, Qingshan Chen, Longhao Kuang; Leucine-rich repeats of PXDN is essential for lens development . Invest. Ophthalmol. Vis. Sci. 2019;60(9):4297. doi: https://doi.org/.
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Mutations in Peroxidasin (PXDN) cause severe inherited eye disorders in humans, such as congenital cataract, corneal opacity and developmental glaucoma. As there are mutiple domains in PXDN, including Leucine-rich repeats (LRR), immunoglobulin domain, peroxidase domain and VW domain. The function of each domain remains unknown. To investigate the role of LRR domain during the eye development and disease, we generated a novel PXDN knockout mice with two exons of LRR domains are deleted and performed preliminary characterization.
CRISPR/Cas9 system was used to make large DNA fragment deletions, including LRR3 and LRR4 domain deletion, about 130-177 aa in size. The eyes of the LRR-deficient mice were analyzed by histology and immunohistochemistry.
We successfully generated a new PXDN knockout mouse line with LRR deficiency, which resulted in the genetic deletion of two exons (LRR3 and LRR4) of the LRR domain. This delete in the two exons causes severe anterior segment dysgenesis and microphthalmia in postnatal periods, which resembles the manifestations in patients with PXDN mutations. During embryonic peroids, the lens capsule is disrupted and broken, and lens matrix is intruded into the anterior chamber.
LRR domain of PXDN is essential for lens development, espically for lens capsule development. Deficiency of LRR domain of the PXDN leads to lens capsule broken (congenital cataract), and later anterior segment dysgenesis and microphthalmia. Our model also gives a pathological mechanism of anterior segment dysgenesis and microphthalmia due to abnormal lens development.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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