International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


K. Weiser
Baylor College of Medicine

Justice MJ
Baylor College of Medicine

In an effort to identify genes involved in leukemogenesis, AKXD mouse strains with Murine Leukemia Virus (MLV) in their germline were screened for leukemia and lymphoma.  The location of somatic insertions was determined by PCR in leukemic animals.  This screen identified sites of frequent integration leading to leukemia in mice.  The most frequent insertion site in these mice is lymphoid viral insertion site 1 (Lvis1) which was rearranged in 22% of B-cell cancers in the initial study.  Although no genes were located in the Lvis1 region, two genes 50-70kb upstream, Hex and Eg5, are upregulated on viral insertion in Lvis1.   Conversely, genes equivalent distances downstream of Lvis1 are not misexpressed. Comparing human and mouse sequence at Lvis1 reveals regions of high identity in Lvis1.  DNaseI hypersensitivity studies reveal possible sites of hypersensitivity in cell lines which normally express Hex.  This indicates that Lvis1 may be a site of trans factor binding correlated with expression of Hex.  We believe that Lvis1 is a genetic control region for Hex and possibly Eg5 and that these genes are part of a pathway that is important for leukemia development.  Creation of reporter constructs to test Lvis1 repressor/enhancer activity will provide clues as to the regulatory activity of this site.  In vivo analysis of alterations at Lvis1 are also needed to determine the exact role of Lvis1 in gene regulation in the mouse.

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