Correlation Engine 2.0
Clear Search sequence regions

  • adult (1)
  • albuminuria (1)
  • brain (1)
  • cone (2)
  • did (1)
  • email (1)
  • epithelium (3)
  • erythrocytosis (1)
  • erythropoietin (2)
  • had (2)
  • heart (1)
  • HIF 1α (1)
  • hypoxia (1)
  • impairment (1)
  • lamellar bodies (1)
  • lung (1)
  • mice (7)
  • neurons (1)
  • normal vision (1)
  • oxygen (1)
  • P4H TM (11)
  • pigment (3)
  • risk factors (1)
  • serum (1)
  • skeletal muscle (1)
  • target genes (1)
  • Sizes of these terms reflect their relevance to your search.

    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. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email:


    Henri Leinonen, Maarit Rossi, Antti M Salo, Päivi Tiainen, Jaana Hyvärinen, Marja Pitkänen, Raija Sormunen, Ilkka Miinalainen, Chi Zhang, Raija Soininen, Kari I Kivirikko, Ari Koskelainen, Heikki Tanila, Johanna Myllyharju, Peppi Koivunen. Lack of P4H-TM in mice results in age-related retinal and renal alterations. Human molecular genetics. 2016 Jul 27

    PMID: 27466183

    View Full Text