Tetracycline-inducible NUP98-HOXD13 (NHD13) transgenic mice are combined with a constitutively activated human &beta;-catenin gene. Mice express the NHD13 fusion gene, which consists of the amino-terminal region of the human nucleoporin 98kDa (NUP98) fused to the homeodomain of the human homeobox D13 (HOXD13) under the control of the mouse vav1 oncogene (Vav1) regulatory elements. The transgene is expressed specifically in hematopoietic tissues and is detected in thymus, spleen, and bone marrow. The fusion gene product (protein) is detected in thymocytes from transgenic mice by Western blot analysis. Hemizygous transgenic mice develop myelodysplastic syndromes (hematopoietic stem cell disorder) with peripheral blood cytopenia and dysplasia and normocellular to hypercellular bone marrow. By 7 months of age, hemizygotes exhibit leukopenia and anemia. Bone marrow transplantation of NHD13/S33Y &beta;-catenin overexpressing cells into lethally irradiated CD45.1+ recipients treated with doxycycline (to activate &beta;-catenin) develop an increase in mature and immature myeloid cells, reduced white blood cell counts and succumb to lethal myeloid disease with a median latency of 388 days, earlier than the 451 days observed in NHD13 transgenic mice. Transplanted mice die mainly of myeloid leukemia (5 out 8) with enlarged spleens and increased white blood cells, the remaining mice die of an MDS-like phenotype. This mutant mouse strain may be useful in studies of myelodysplastic syndromes, precursor T cell lymphoblastic leukemia/lymphoma (pre-T LBL) and acute myeloid leukemia. Of note, the NHD13 transgene [Tg(Vav1-NUP98/HOXD13)G2Apla] alone is distributed as Stock No. <a href="https://www.jax.org/strain/010505">010505</a>. The R26-M2rtTA allele has widespread expression of an optimized reverse tetracycline-controlled transactivator (rtTA-M2), and is available alone as Stock No. <a href="https://www.jax.org/strain/006965">006965</a>.

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This strain combines the NUP98-HOXD13 (NHD13) transgene with a doxycycline-inducible constitutively activated human &beta;-catenin. NHD13 expresses human nucleoporin fused to human homeobox D13 under the control of the vav1 oncogene in hematopoietic tissues and is a mouse model of myelodysplastic syndrome. Overexpression of &beta;-catenin in NHD13 mice results in accelerated myeloid disease progression and an increased likelihood of transformation. This mutant mouse strain may be useful in studies of myelodysplastic syndromes, precursor T cell lymphoblastic leukemia/lymphoma (pre-T LBL) and acute myeloid leukemia. Of note, the NHD13 transgene [Tg(Vav1-NUP98/HOXD13)G2Apla] alone is distributed as Stock No. <a href="https://www.jax.org/strain/010505">010505</a>. The R26-M2rtTA allele has widespread expression of an optimized reverse tetracycline-controlled transactivator (rtTA-M2), and is available alone as Stock No. <a href="https://www.jax.org/strain/006965">006965</a>.

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