RGD Reference Report - Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure. - Rat Genome Database

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Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure.

Authors: Minamishima, YA  Moslehi, J  Bardeesy, N  Cullen, D  Bronson, RT  Kaelin WG, JR 
Citation: Minamishima YA, etal., Blood. 2008 Mar 15;111(6):3236-44. Epub 2007 Dec 20.
RGD ID: 11251770
Pubmed: PMID:18096761   (View Abstract at PubMed)
PMCID: PMC2265460   (View Article at PubMed Central)
DOI: DOI:10.1182/blood-2007-10-117812   (Journal Full-text)

Pharmacologic activation of the heterodimeric HIF transcription factor appears promising as a strategy to treat diseases, such as anemia, myocardial infarction, and stroke, in which tissue hypoxia is a prominent feature. HIF accumulation is normally linked to oxygen availability because an oxygen-dependent posttranslational modification (prolyl hydroxylation) marks the HIFalpha subunit for polyubiquitination and destruction. Three enzymes (PHD1, PHD2, and PHD3) capable of catalyzing this reaction have been identified, although PHD2 (also called Egln1) appears to be the primary HIF prolyl hydroxylase in cell culture experiments. We found that conditional inactivation of PHD2 in mice is sufficient to activate a subset of HIF target genes, including erythropoietin, leading to striking increases in red blood cell production. Mice lacking PHD2 exhibit premature mortality associated with marked venous congestion and dilated cardiomyopathy. The latter is likely the result of hyperviscosity syndrome and volume overload, although a direct effect of chronic, high-level HIF stimulation on cardiac myocytes cannot be excluded.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dilated cardiomyopathy  ISOEgln1 (Mus musculus)11251770; 11251770 RGD 
dilated cardiomyopathy  IMP 11251770 RGD 
Hyperemia  ISOEgln1 (Mus musculus)11251770; 11251770 RGD 
Hyperemia  IMP 11251770 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Egln1  (egl-9 family hypoxia-inducible factor 1)

Genes (Mus musculus)
Egln1  (egl-9 family hypoxia-inducible factor 1)

Genes (Homo sapiens)
EGLN1  (egl-9 family hypoxia inducible factor 1)


Additional Information