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Accession IconSRP077870

HIF-1a activation is sufficient for the development of MDS

Organism Icon Mus musculus
Sample Icon 4 Downloadable Samples
Technology Badge IconIllumina HiSeq 1000

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Description
Hypoxia inducible factor-1a (HIF-1a) is a critical transcription factor for the hypoxic response, angiogenesis, normal hematopoietic stem cell regulation, and cancer development. Importantly, HIF-1a is also a key regulator for immune cell activation. In order to determine whether HIF-1a is sufficient for developing MDS phenotypes, we generated blood specific inducible HIF-1a transgenic mice. Using Vav1-Cre/Rosa26-loxP-Stop-loxP (LSL) rtTA driver, stable HIF-1a can be induced in a doxycycline administration dependent manner. After induction, HIF-1a-induced mice developed thrombocytopenia, leukocytopenia, macrocytic anemia, and multi-lineage dysplasia. We also found activation of both innate and adaptive immunity in HIF-1a- induced mice compared to those from control mice. Taken together, these data suggest that HIF-1a is sufficient to trigger a variety of key MDS features Overall design: Expression profiles of mRNA in HSPCs from constitutively active form of HIF1a protein induced mice and their control mice.
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4
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