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| Status |
Public on Feb 06, 2011 |
| Title |
HMGA2 overexpression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Overexpression of high mobility group AT-hook 2 (HMGA2) associated with truncations of its 3’ untranslated region (UTR) with let-7 micro RNA-complementary sequences have been identified in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we generated transgenic mice (∆Hmga2 mice) with a 3’UTR-trncated Hmga2 cDNA that overexpress Hmga2 mRNA and protein in hematopoietic organs. ∆Hmga2 mice showed proliferative hematopoiesis that mimicked a myeloproliferative neoplasm (MPN)-like phenotype with increased numbers of all lineages of peripheral blood cells, hypercellular bone marrow (BM), splenomegaly with extramedullary erythropoiesis, and erythropoietin-independent erythroid colony formation compared to wild-type mice. ∆Hmga2 BM-derived cells took over most of hematopoiesis in competitive repopulations during serial BM transplants. When we bred mice with circulating PNH cells (Piga- mice) with ∆Hmga2 mice, the lack of GPI-linked proteins did not add an additional clonal advantage to the ∆Hmga2+ cells. In summary, our results showed that the overexpression of a 3’UTR-truncated Hmga2 leads to a proliferative hematopoiesis with clonal advantage, which may explain clonal expansion in PNH or MPN at the level of HSC.
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| Overall design |
Eight independent preparations of RNA, which included each 2 samples of KLS cells and MEP cells from ∆Hmga2 mice and 2 each from WT mice. Each preparation was made from 4 or 6 mice.
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| Contributor(s) |
Ikeda K, Mason PJ, Bessler M |
| Citation(s) |
21460244 |
| Submission date |
Sep 10, 2010 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Kazuhiko Ikeda |
| E-mail(s) |
kazu-ike@fmu.ac.jp
|
| Organization name |
Fukushima Medical University
|
| Department |
Blood Transfusion and Transplantation Immunology
|
| Street address |
1 Hikariga-oka
|
| City |
Fukushima |
| State/province |
Fukushima |
| ZIP/Postal code |
960-1295 |
| Country |
Japan |
| |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA130239 |
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