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N. F. Schaefer, U. F. O. Luhmann, S. Feil, W. Berger; Differential Gene Expression in Ndph Knockout Mice in Retinal Development. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3444. doi: https://doi.org/.
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Angiogenesis, the process of blood vessel development from an already existing vasculature, is essential for organogenesis in order to provide oxygen and nutrition supply for still evolving structures. Mutations in the NDP gene seem to impair angiogenesis in the eyes of patients diagnosed with a type of blindness belonging to the group of exudative vitreoretinopathies. With this study, we wanted to investigate the primary defects caused by the absence of Norrin (the NDP protein) in the developing mouse retina.
A comparative gene expression analysis was performed on p7 (postnatal day 7) retinae from a knockout mouse model for Norrie disease. Differential gene expression in wild type versus knockout mice was determined using Affymetrix microarrays (GeneChip® Mouse Genome 430 2.0 Array) . Subsequently, results were verified by quantitative real-time PCR analyses. Immunohistochemistry was performed for the vascular permeability marker Plvap and Collagen type IV.
Our study identified transcriptional differences in Ndphy/- vs. wild type mice retinae at p7. Expression of the neutral amino acid transporter Slc38a5, apolipoprotein D (ApoD) and angiotensin receptor-like 1 (Agtrl1) was decreased in the knockout, whereas transcript levels for adrenomedullin (Adm) and the plasmalemma vesicle associated protein (Plvap) were increased in comparison to the wild type.
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 NDP knockout mice and reflect or may contribute to the pathogenesis of the disease.
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