Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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
_version_ 1782221463287234560
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
work_keys_str_mv AT chenjing retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice
AT stahlandreas retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice
AT krahnathanm retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice
AT seawardmollyr retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice
AT joyaljeansebastian retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice
AT juanaimeem retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice
AT hattoncolmanj retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice
AT adermanchristopherm retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice
AT dennisonrobertaj retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice
AT willettkeirnanl retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice
AT sapiehaprzemyslaw retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice
AT smithloiseh retinalexpressionofwntpathwaymediatedgenesinlowdensitylipoproteinreceptorrelatedprotein5lrp5knockoutmice