International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


A Castillo
Baylor College of Medicine

Justice MJ
Baylor College of Medicine

AKXD recombinant inbred (RI) mice are susceptible to developing a variety of leukemias and lymphomas, which are associated with somatically acquired proviruses.  These proviruses integrate throughout the genome activating cellular proto-oncogenes and/or disrupting tumor suppressor genes, thereby leading to tumorigenesis.  Multiple common sites of integration have been identified in mice, but recently a novel site of integration, lymphoid viral insertion site (Lvis1), was identified and shown to be the most common site of integration found in tumor samples taken from AKXD RI mice. Analysis of gene expression in the region of Lvis1 showed two genes, Hex and Eg5, whose expression levels were altered in tumors containing retroviral integrations at Lvis1.  Hex is a divergent homeobox gene expressed during embryogenesis and in B-cell and myeloid cell lineages in the adult mouse.  Eg5 is a member of the bim-c kinesin like motor protein family and is believed to be involved in mitotic spindle formation and stabilization. Our goal is to test the hypothesis that Hex and/or Eg5 can act as an oncogene when overexpressed.  The approach I have taken is to generate transgenic mice, which overexpress Eg5 in hematopoietic tissues, to determine if misexpression of Eg5 alone is capable of inducing tumors.  Our second approach is to transduce bone marrow cells with Eg5 carrying retroviruses for transplantation into irradiated mice, and analyze the recipients for abnormalities in differentiation and the increased incidence of lymphomas. Additionally, functional analysis will be performed to better understand the cellular and tumorigenic function of Eg5.

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