Next Article in Journal
Windup of Nociceptive Flexion Reflex Depends on Synaptic and Intrinsic Properties of Dorsal Horn Neurons in Adult Rats
Previous Article in Journal
Discovery of a Highly Selective MC1R Agonists Pentapeptide to Be Used as a Skin Pigmentation Enhancer and with Potential Anti-Aging Properties
Open AccessArticle

Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation

1
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
2
Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
3
Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul 06591, Korea
4
Department of Genetic Engineering Mouse, Macrogen Inc, Seoul 08511, Korea
5
Korea Mouse Sensory Phenotyping Center (KMSPC), Yonsei University College of Medicine, Seoul 03722, Korea
6
Institute for Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Korea
7
Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea
8
Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(24), 6144; https://doi.org/10.3390/ijms20246144
Received: 24 September 2019 / Revised: 22 November 2019 / Accepted: 3 December 2019 / Published: 5 December 2019
(This article belongs to the Section Molecular Genetics and Genomics)
Peroxidasin (PXDN) is a unique peroxidase containing extracellular matrix motifs and stabilizes collagen IV networks by forming sulfilimine crosslinks. PXDN gene knockout in Caenorhabditis elegans (C. elegans) and Drosophila results in the demise at the embryonic and larval stages. PXDN mutations lead to severe eye disorders, including microphthalmia, cataract, glaucoma, and anterior segment dysgenesis in humans and mice. To investigate how PXDN loss of function affects organ development, we generated Pxdn knockout mice by deletion of exon 1 and its 5′ upstream sequences of the Pxdn gene using the CRISPR/Cas9 system. Loss of both PXDN expression and collagen IV sulfilimine cross-links was detected only in the homozygous mice, which showed completely or almost closed eyelids with small eyes, having no apparent external morphological defects in other organs. In histological analysis of eye tissues, the homozygous mice had extreme defects in eye development, including no eyeballs or drastically disorganized eye structures, whereas the heterozygous mice showed normal eye structure. Visual function tests also revealed no obvious functional abnormalities in the eyes between heterozygous mice and wild-type mice. Thus, these results suggest that PXDN activity is essential in eye development, and also indicate that a single allele of Pxdn gene is sufficient for eye-structure formation and normal visual function. View Full-Text
Keywords: peroxidasin; knockout mice; anophthalmia; microphthalmia; eye development; CRISPR/Cas9 peroxidasin; knockout mice; anophthalmia; microphthalmia; eye development; CRISPR/Cas9
Show Figures

Figure 1

MDPI and ACS Style

Kim, H.-K.; Ham, K.A.; Lee, S.-W.; Choi, H.S.; Kim, H.-S.; Kim, H.K.; Shin, H.-S.; Seo, K.Y.; Cho, Y.; Nam, K.T.; Kim, I.-B.; Joe, Y.A. Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation. Int. J. Mol. Sci. 2019, 20, 6144.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop