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Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice
Mutations in low-density lipoprotein receptor-related protein 5 (Lrp5) impair retinal angiogenesis in patients with familial exudative vitreoretinopathy (FEVR), a rare type of blinding vascular eye disease. The defective retinal vasculature phenotype in human FEVR patients is recapitulated in Lrp5 k...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260226/ https://www.ncbi.nlm.nih.gov/pubmed/22272305 http://dx.doi.org/10.1371/journal.pone.0030203 |
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author | Chen, Jing Stahl, Andreas Krah, Nathan M. Seaward, Molly R. Joyal, Jean-Sebastian Juan, Aimee M. Hatton, Colman J. Aderman, Christopher M. Dennison, Roberta J. Willett, Keirnan L. Sapieha, Przemyslaw Smith, Lois E. H. |
author_facet | Chen, Jing Stahl, Andreas Krah, Nathan M. Seaward, Molly R. Joyal, Jean-Sebastian Juan, Aimee M. Hatton, Colman J. Aderman, Christopher M. Dennison, Roberta J. Willett, Keirnan L. Sapieha, Przemyslaw Smith, Lois E. H. |
author_sort | Chen, Jing |
collection | PubMed |
description | Mutations in low-density lipoprotein receptor-related protein 5 (Lrp5) impair retinal angiogenesis in patients with familial exudative vitreoretinopathy (FEVR), a rare type of blinding vascular eye disease. The defective retinal vasculature phenotype in human FEVR patients is recapitulated in Lrp5 knockout (Lrp5(−/−)) mouse with delayed and incomplete development of retinal vessels. In this study we examined gene expression changes in the developing Lrp5(−/−) mouse retina to gain insight into the molecular mechanisms that underlie the pathology of FEVR in humans. Gene expression levels were assessed with an Illumina microarray on total RNA from Lrp5(−/−) and WT retinas isolated on postnatal day (P) 8. Regulated genes were confirmed using RT-qPCR analysis. Consistent with a role in vascular development, we identified expression changes in genes involved in cell-cell adhesion, blood vessel morphogenesis and membrane transport in Lrp5(−/−) retina compared to WT retina. In particular, tight junction protein claudin5 and amino acid transporter slc38a5 are both highly down-regulated in Lrp5(−/−) retina. Similarly, several Wnt ligands including Wnt7b show decreased expression levels. Plasmalemma vesicle associated protein (plvap), an endothelial permeability marker, in contrast, is up-regulated consistent with increased permeability in Lrp5(−/−) retinas. Together these data suggest that Lrp5 regulates multiple groups of genes that influence retinal angiogenesis and may contribute to the pathogenesis of FEVR. |
format | Online Article Text |
id | pubmed-3260226 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32602262012-01-23 Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice Chen, Jing Stahl, Andreas Krah, Nathan M. Seaward, Molly R. Joyal, Jean-Sebastian Juan, Aimee M. Hatton, Colman J. Aderman, Christopher M. Dennison, Roberta J. Willett, Keirnan L. Sapieha, Przemyslaw Smith, Lois E. H. PLoS One Research Article Mutations in low-density lipoprotein receptor-related protein 5 (Lrp5) impair retinal angiogenesis in patients with familial exudative vitreoretinopathy (FEVR), a rare type of blinding vascular eye disease. The defective retinal vasculature phenotype in human FEVR patients is recapitulated in Lrp5 knockout (Lrp5(−/−)) mouse with delayed and incomplete development of retinal vessels. In this study we examined gene expression changes in the developing Lrp5(−/−) mouse retina to gain insight into the molecular mechanisms that underlie the pathology of FEVR in humans. Gene expression levels were assessed with an Illumina microarray on total RNA from Lrp5(−/−) and WT retinas isolated on postnatal day (P) 8. Regulated genes were confirmed using RT-qPCR analysis. Consistent with a role in vascular development, we identified expression changes in genes involved in cell-cell adhesion, blood vessel morphogenesis and membrane transport in Lrp5(−/−) retina compared to WT retina. In particular, tight junction protein claudin5 and amino acid transporter slc38a5 are both highly down-regulated in Lrp5(−/−) retina. Similarly, several Wnt ligands including Wnt7b show decreased expression levels. Plasmalemma vesicle associated protein (plvap), an endothelial permeability marker, in contrast, is up-regulated consistent with increased permeability in Lrp5(−/−) retinas. Together these data suggest that Lrp5 regulates multiple groups of genes that influence retinal angiogenesis and may contribute to the pathogenesis of FEVR. Public Library of Science 2012-01-17 /pmc/articles/PMC3260226/ /pubmed/22272305 http://dx.doi.org/10.1371/journal.pone.0030203 Text en Chen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Chen, Jing Stahl, Andreas Krah, Nathan M. Seaward, Molly R. Joyal, Jean-Sebastian Juan, Aimee M. Hatton, Colman J. Aderman, Christopher M. Dennison, Roberta J. Willett, Keirnan L. Sapieha, Przemyslaw Smith, Lois E. H. Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice |
title | Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice |
title_full | Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice |
title_fullStr | Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice |
title_full_unstemmed | Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice |
title_short | Retinal Expression of Wnt-Pathway Mediated Genes in Low-Density Lipoprotein Receptor-Related Protein 5 (Lrp5) Knockout Mice |
title_sort | retinal expression of wnt-pathway mediated genes in low-density lipoprotein receptor-related protein 5 (lrp5) knockout mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260226/ https://www.ncbi.nlm.nih.gov/pubmed/22272305 http://dx.doi.org/10.1371/journal.pone.0030203 |
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