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

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 le...

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Autores principales: Kim, Hyun-Kyung, Ham, Kyung A, Lee, Seung-Woo, Choi, Hong Seok, Kim, Hong-Sug, Kim, Hong Kyung, Shin, Hae-Sol, Seo, Kyoung Yul, Cho, Yejin, Nam, Ki Taek, Kim, In-Beom, Joe, Young Ae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941041/
https://www.ncbi.nlm.nih.gov/pubmed/31817535
http://dx.doi.org/10.3390/ijms20246144
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author Kim, Hyun-Kyung
Ham, Kyung A
Lee, Seung-Woo
Choi, Hong Seok
Kim, Hong-Sug
Kim, Hong Kyung
Shin, Hae-Sol
Seo, Kyoung Yul
Cho, Yejin
Nam, Ki Taek
Kim, In-Beom
Joe, Young Ae
author_facet Kim, Hyun-Kyung
Ham, Kyung A
Lee, Seung-Woo
Choi, Hong Seok
Kim, Hong-Sug
Kim, Hong Kyung
Shin, Hae-Sol
Seo, Kyoung Yul
Cho, Yejin
Nam, Ki Taek
Kim, In-Beom
Joe, Young Ae
author_sort Kim, Hyun-Kyung
collection PubMed
description 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.
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spelling pubmed-69410412020-01-09 Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation Kim, Hyun-Kyung Ham, Kyung A Lee, Seung-Woo Choi, Hong Seok Kim, Hong-Sug Kim, Hong Kyung Shin, Hae-Sol Seo, Kyoung Yul Cho, Yejin Nam, Ki Taek Kim, In-Beom Joe, Young Ae Int J Mol Sci Article 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. MDPI 2019-12-05 /pmc/articles/PMC6941041/ /pubmed/31817535 http://dx.doi.org/10.3390/ijms20246144 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Hyun-Kyung
Ham, Kyung A
Lee, Seung-Woo
Choi, Hong Seok
Kim, Hong-Sug
Kim, Hong Kyung
Shin, Hae-Sol
Seo, Kyoung Yul
Cho, Yejin
Nam, Ki Taek
Kim, In-Beom
Joe, Young Ae
Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation
title Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation
title_full Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation
title_fullStr Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation
title_full_unstemmed Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation
title_short Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation
title_sort biallelic deletion of pxdn in mice leads to anophthalmia and severe eye malformation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941041/
https://www.ncbi.nlm.nih.gov/pubmed/31817535
http://dx.doi.org/10.3390/ijms20246144
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