International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 171 - Looking for a tumor suppressor gene of murine acute myeloid leukemia using the chromosome 2 deletion-mutants

Yumiko Nitta, Ph.D.,
Res. Inst. Radiat. Biol. Medicine
Hiroshima University
Kasumi 1-2-3
Minami-ku
Hiroshima 734-8553
Japan

Co-Authors: Kazuko Yoshida, Ph.D.,
Institutions: National Institute Radiol. Science

Radiation-induced murine acute myeloid leukemia (AML) is characterized by the chromosome 2 deletions (1983). The minimally deleted region (mdr) is between the D2Mit126 and D2Mit185, which is homologous to the human chromosome 11p11-12. We expect an AML suppressor gene to map within the mdr, while, Kominami proposes a lymphoma susceptibility gene within the same region (2000). First, we performed the deletion-wide screen on AMLs stored in the NIRS, Chiba, JAPAN to confirm the association of the mdr-deletion with the AML-development. FISHing on the 105 AMLs showed hemizygous deletion of the D(2)Mit15 in 97 cases (92.4%).Second, we have discovered the three mutants in the mouse embryo bank, Harwell, MRC, UK, Del(2)59H, Del(2)Sey3H and Del(2)Sey4H, which delete the mdr loci. Original germ line mutations had been induced by γ-irradiation and carried out hemizygously in the hybrid mouse of C3H/He x 101. A female of the Del(2)59H developed spontaneous erythroleukemia during the life-span observation. Testing the radiation-induced leukemogenicity on these mutants has started to make sure whether the development of murine AML would be explained by the classic tumor suppressor gene-mechanism.


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