| http://purl.uniprot.org/citations/27466183 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27466183 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27466183 | http://www.w3.org/2000/01/rdf-schema#comment | "Age-related macular degeneration (AMD), affecting the retinal pigment epithelium (RPE), is the leading cause of blindness in middle-aged and older people in developed countries. Genetic and environmental risk factors have been identified, but no effective cure exists. Using a mouse model we show that a transmembrane prolyl 4-hydroxylase (P4H-TM), which participates in the oxygen-dependent regulation of the hypoxia-inducible factor (HIF), is a potential novel candidate gene for AMD. We show that P4h-tm had its highest expression levels in the mouse RPE and brain, heart, lung, skeletal muscle and kidney. P4h-tm-/- mice were fertile and had a normal life span. Lack of P4h-tm stabilized HIF-1α in cortical neurons under normoxia, while in hypoxia it increased the expression of certain HIF target genes in tissues with high endogenous P4h-tm expression levels more than in wild-type mice. Renal erythropoietin levels increased in P4h-tm-/- mice with aging, but the resulting ∼2-fold increase in erythropoietin serum levels did not lead to erythrocytosis. Instead, accumulation of lipid-containing lamellar bodies in renal tubuli was detected in P4h-tm-/- mice with aging, resulting in inflammation and fibrosis, and later glomerular sclerosis and albuminuria. Lack of P4h-tm was associated with retinal thinning, rosette-like infoldings and drusen-like structure accumulation in RPE with aging, as is characteristic of AMD. Photoreceptor recycling was compromised, and electroretinograms revealed functional impairment of the cone pathway in adult P4h-tm-/- mice and cone and rod deficiency in middle-aged mice. P4H-TM is therefore imperative for normal vision, and potentially a novel candidate for age-induced diseases, such as AMD."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddw228"xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddw228"xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Rossi M."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Rossi M."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Zhang C."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Zhang C."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Myllyharju J."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Myllyharju J."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Tanila H."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Tanila H."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Koivunen P."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Koivunen P."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Tiainen P."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Tiainen P."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Kivirikko K.I."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Kivirikko K.I."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Soininen R."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Soininen R."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Sormunen R."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Sormunen R."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Miinalainen I."xsd:string |
| http://purl.uniprot.org/citations/27466183 | http://purl.uniprot.org/core/author | "Miinalainen I."xsd:string |