Dataset Information


The role of HIF in FH-associated renal neoplasia

ABSTRACT: Fumarate hydratase (FH) mutations predispose to renal cysts cancer. These cancers overexpress hypoxia-inducible factor-alpha (Hif-1a). We have generated a conditional Fh1 (mouse FH) knockout mice that develop renal cysts and overexpress Hif-1a. In order to identify the contribution of Hif-1a to cyst formation we have intercrossed our mice with conditional HIf-1a KO mice. We intercrossed Fh1/Hif1a mice with kidney specific cre recombinase (Ksp-Cre) and analysed kidney cyst formation. RNA was extracted from cysts from 4xFh1 KO, 4xFh1/Hif-1a KO and 4 control mice. For each comparison littermates were used and the animals were aged 15 weeks i.e. early cystic disease.

ORGANISM(S): Mus musculus  

SUBMITTER: Dilair Baban   Natasha Sahgal  Peter Ratcliffe  Emine Hatipoglu  Emma Nye  Benedikt Kessler  Gordon Stamp  Nicola Ternette  Linda O'Flaherty  Chris Pugh  Mona El-Bahrawy  Norma Frizzell  Helen Lockstone  Julie Adam  Patrick Pollard 

PROVIDER: E-GEOD-29988 | ArrayExpress | 2011-10-23



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The Krebs cycle enzyme fumarate hydratase (FH) is a human tumor suppressor whose inactivation is associated with the development of leiomyomata, renal cysts, and tumors. It has been proposed that activation of hypoxia inducible factor (HIF) by fumarate-mediated inhibition of HIF prolyl hydroxylases drives oncogenesis. Using a mouse model, we provide genetic evidence that Fh1-associated cyst formation is Hif independent, as is striking upregulation of antioxidant signaling pathways revealed by ge  ...[more]

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