Hottip (Hoxa distal transcript antisense RNA) encodes a long non-coding RNA (lncRNA) that functions as an epigenetic regulator of the HOXA genes. Hottip lncRNA is aberrantly activated in acute myeloid leukemia (AML) and is involved in the leukemic transformation of hematopoietic stem cells . Hottip-Tg transgenic mice express mouse Hottip in hematopoietic cells through vav 1 oncogene promoter/control regions. Hemizygous Hottip-Tg mice are viable and fertile and exhibit increased white blood cell and neutrophil counts, splenomegaly, increased numbers of immature myeloid cells, myeloid infiltration in the liver, as well as increased frequencies and numbers of long and short term hematopoietic stem cells (HSC). Thirty-three percent of hemizygotes die by 18 months. Homozygous HottipHomo-Tg mice develop a more severe phenotype including: severe anemia, splenomegaly, and increased numbers of immature myeloid cells in the bone marrow. Fifty percent of homozygous mice develop AML-like disease and die by 8 months.

Hottip-Tg transgenic mice express mouse Hottip (Hoxa distal transcript antisense RNA) in hematopoietic cells and tissues. Mice develop anemia, splenomegaly, increased numbers of immature myeloid and die prematurely. These mice may be useful for the study of acute myeloid leukemia.

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