Effects of a Hemizygous Deletion of Mouse Chromosome 2 on the Hematopoietic and Intestinal Tumorigenesis

抄録

Allelic loss of chromosome 2 is associated with radiation-induced murine acute myeloid leukemia. However, the gene, which contributes mainly to the leukemogenesis in a tumor suppression manner, has not been identified, yet. Expecting predisposition to acute myeloid leukemia, a radiation leukemogenensis experiment was performed with Pax6^Sey3H, one of the small eye mutants. Deletion mapping of Pax6^Sey3H indicated that the deleted segment extended from 106.00 to 111.47 Mb from the centromere with a length of 5.47 Mb on chromosome 2. Six known and seventeen novel genes were located in the segment. Pax6^Sey3H mutants crossed back into C3H/He did not develop hematopoietic tumors spontaneously, but they did after exposure to γ-rays. The final incidence of hematopoietic tumor in mutants (45.2%) was higher than that in normal sibs (26.2%), and the survival curve of mutants shifted toward the left (p<0.05 by the Cox-Mantel test). Mutants developed intestinal tumors spontaneously with long latency as well as showing abnormality in the Wirsung’s duct from young ages. Congenital deletion of the 5.47 Mb segment at the middle region on chromosome 2 alone did not trigger hematopoietic tumors, however, the deletion promoted the development of hematopoietic tumors initiated by radiation. The deletion developed intestinal tumors spontaneously. Radiation exposure at 10 weeks of age did not contribute to the intestinal tumorigenesis.