This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cadieux, C. Articles by Nepveu, A. Search for Related Content PubMed PubMed Citation Articles by Cadieux, C. Articles by Nepveu, A.

Transgenic Mice Expressing the p75 CCAAT-Displacement Protein/Cut Homeobox Isoform Develop a Myeloproliferative Disease–Like Myeloid Leukemia

¹ Molecular Oncology Group, McGill University Health Center, Departments of ² Biochemistry, ³ Oncology, ⁴ Medicine, ⁵ Microbiology and Immunology, ⁶ Human Genetics, and ⁷ Pathology, McGill University; ⁸ McConnell Brain Imaging Centre, Montreal Neurological Institute; and Departments of ⁹ Pathology and ¹⁰ Microbiology, Faculty of Veterinary Medicine, Université de Montréal, Montreal, Quebec, Canada

Requests for reprints: Alain Nepveu, Molecular Oncology Group, McGill University, 687 Pine Avenue West, Room H5.21, Montreal, Quebec, Canada H3A 1A1. Phone: 514-934-1934 ext. 35842; Fax: 514-843-1478; E-mail: alain.nepveu{at}mcgill.ca.

The p75 CCAAT-displacement protein/Cut homeobox (CDP/Cux) isoform was previously reported to be overexpressed in human breast cancers. To investigate its oncogenic potential, we engineered two transgenic mouse lines expressing p75 CDP/Cux under the control of the mouse mammary tumor virus-long terminal repeat. The FVB strain of mouse is generally used in the generation of mouse models for breast cancer. The transgene was introduced into the hprt locus of 129/Ola embryonic stem cells and, following germ line passage, was backcrossed onto the FVB and C57BL/6 mouse strains. Here, we describe the phenotype of p75 CDP/Cux transgenic virgin female mice of the first backcross generations. We report that after a long latency period, 33% of mice from two independent transgenic lines and from backcrosses into either the FVB or the C57BL/6 strains succumbed to a similar disease characterized by splenomegaly, hepatomegaly, and frequent infiltration of leukocytes into nonhematopoietic organs like the kidneys and lungs. Although an excess of B or T cells was observed in three diseased mice, in 17 other cases, histologic and flow cytometry analyses revealed the expansion of a population of neutrophils in the blood, spleen, and bone marrow. The increase in neutrophils correlated with signs of anemia and thrombocytopenia, whereas there was no indication of a reactive process. Therefore, p75 CDP/Cux transgenic mice displayed heightened susceptibility to a disease defined as a myeloproliferative disease–like myeloid leukemia. These results indicate that the overexpression of p75 CDP/Cux could alter homeostasis in the hematopoietic compartment. (Cancer Res 2006; 66(19): 9492-501)

This article has been cited by other articles:

				C. Cadieux, V. Kedinger, L. Yao, C. Vadnais, M. Drossos, M. Paquet, and A. Nepveu Mouse Mammary Tumor Virus p75 and p110 CUX1 Transgenic Mice Develop Mammary Tumors of Various Histologic Types Cancer Res., September 15, 2009; 69(18): 7188 - 7197. [Abstract] [Full Text] [PDF]

				C. Cadieux, R. Harada, M. Paquet, O. Cote, M. Trudel, A. Nepveu, and M. Bouchard Polycystic Kidneys Caused by Sustained Expression of Cux1 Isoform p75 J. Biol. Chem., May 16, 2008; 283(20): 13817 - 13824. [Abstract] [Full Text] [PDF]

				M. Truscott, R. Harada, C. Vadnais, F. Robert, and A. Nepveu p110 CUX1 Cooperates with E2F Transcription Factors in the Transcriptional Activation of Cell Cycle-Regulated Genes Mol. Cell. Biol., May 15, 2008; 28(10): 3127 - 3138. [Abstract] [Full Text] [PDF]

				B. Goulet, Y. Markovic, L. Leduy, and A. Nepveu Proteolytic Processing of Cut Homeobox 1 by Neutrophil Elastase in the MV4;11 Myeloid Leukemia Cell Line Mol. Cancer Res., April 1, 2008; 6(4): 644 - 653. [Abstract] [Full Text] [PDF]

				R. Harada, C. Vadnais, L. Sansregret, L. Leduy, G. Berube, F. Robert, and A. Nepveu Genome-wide location analysis and expression studies reveal a role for p110 CUX1 in the activation of DNA replication genes Nucleic Acids Res., January 17, 2008; 36(1): 189 - 202. [Abstract] [Full Text] [PDF]

				B. Goulet, L. Sansregret, L. Leduy, M. Bogyo, E. Weber, S. S. Chauhan, and A. Nepveu Increased Expression and Activity of Nuclear Cathepsin L in Cancer Cells Suggests a Novel Mechanism of Cell Transformation Mol. Cancer Res., September 1, 2007; 5(9): 899 - 907. [Abstract] [Full Text] [PDF]