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Differential gene expression in Ndph knockout mice in retinal development


Schäfer, N F; Luhmann, U F O; Feil, S; Berger, W (2009). Differential gene expression in Ndph knockout mice in retinal development. Investigative Ophthalmology and Visual Science, 50(2):906-916.

Abstract

PURPOSE. Mutations in the NDP gene impair angiogenesis in the eyes of patients diagnosed with a type of blindness belonging to the group of exudative vitreoretinopathies. With this study, we aimed to investigate differential gene expression caused by the absence of Norrin (the NDP protein) in the developing mouse retina to elucidate early pathogenic events. METHODS. A comparative gene expression analysis was performed on p7 (postnatal day 7) retinae from a knockout mouse model for Norrie disease using Affymetrix microarrays. Subsequently, results were verified by quantitative real-time PCR analyses. Immunohistochemistry was performed for the vascular permeability marker Plasmalemma vesicle-associated protein (Plvap). RESULTS. Our study identified expression differences in Ndph(y/-) vs. wild type mice retinae at p7. Gene transcription of the neutral amino acid transporter Slc38a5, apolipoprotein D (ApoD) and angiotensin II receptor-like 1 (Agtrl1) was decreased in the knockout, whereas transcript levels of adrenomedullin (Adm) and of the plasmalemma vesicle associated protein (Plvap) were increased in comparison to the wild type. In addition, we found ectopic expression of Plvap in the developing retinal vasculature of Norrin knockout mice on the protein level. CONCLUSIONS. These data provide molecular evidence for a role of Norrin in the development of the retinal vasculature. Expression of two genes, Plvap and Slc38a5, is considerably altered in retinal development of Norrin knockout mice and may reflect or contribute to the pathogenesis of the disease. In particular, ectopic expression of Plvap is consistent with hallmark disease symptoms in mouse and man.

Abstract

PURPOSE. Mutations in the NDP gene impair angiogenesis in the eyes of patients diagnosed with a type of blindness belonging to the group of exudative vitreoretinopathies. With this study, we aimed to investigate differential gene expression caused by the absence of Norrin (the NDP protein) in the developing mouse retina to elucidate early pathogenic events. METHODS. A comparative gene expression analysis was performed on p7 (postnatal day 7) retinae from a knockout mouse model for Norrie disease using Affymetrix microarrays. Subsequently, results were verified by quantitative real-time PCR analyses. Immunohistochemistry was performed for the vascular permeability marker Plasmalemma vesicle-associated protein (Plvap). RESULTS. Our study identified expression differences in Ndph(y/-) vs. wild type mice retinae at p7. Gene transcription of the neutral amino acid transporter Slc38a5, apolipoprotein D (ApoD) and angiotensin II receptor-like 1 (Agtrl1) was decreased in the knockout, whereas transcript levels of adrenomedullin (Adm) and of the plasmalemma vesicle associated protein (Plvap) were increased in comparison to the wild type. In addition, we found ectopic expression of Plvap in the developing retinal vasculature of Norrin knockout mice on the protein level. CONCLUSIONS. These data provide molecular evidence for a role of Norrin in the development of the retinal vasculature. Expression of two genes, Plvap and Slc38a5, is considerably altered in retinal development of Norrin knockout mice and may reflect or contribute to the pathogenesis of the disease. In particular, ectopic expression of Plvap is consistent with hallmark disease symptoms in mouse and man.

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18 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Molecular Genetics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:February 2009
Deposited On:14 Jan 2009 10:15
Last Modified:05 Apr 2016 12:46
Publisher:Association for Research in Vision and Ophthalmology
ISSN:0146-0404
Publisher DOI:https://doi.org/10.1167/iovs.08-1731
Official URL:http://www.iovs.org/
PubMed ID:18978344

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