Intestinal tumorigenicity of mice carrying hemizygous Pax6, Pax6(Sey-4H).
The genotype-phenotype relationship in mice was examined experimentally using one of the small eye mutants, Pax6(Sey-4H), which deletes the chromosome 2 middle region, hemizygously. The genotyping indicated that the deleted region starts at a site 102.60 Mb from the centromere and has a length of 6.51 Mb, in which 12 known and 27 novel genes are located. Expecting the development of myeloid leukemia, gamma-irradiation was performed to female mutants at the age of 10 weeks. The mutants did not develop myeloid leukemia during the observation period of 18 months. Instead, they developed tumors in the alimentary tract spontaneously (56.0%). The tumor latency was shortened by the radiation exposure, but the tumor incidence of the gamma-irradiated group (62.5%) was as high as that of spontaneously developing tumors. Intraductal proliferation of the epithelium of the Wirsung duct was observed in the gamma-irradiated mutants (18.8%). Considering the results of the Pax6(Sey-4H) mutant together with those of another small eye mutant, Pax6(Sey-3H), the anomaly and the tumorigenicity of the intestinal tract were closely related to the hemizygosity of the 3.2 Mb segment of chromosome 2, where both mutants show a common deletion.
International Radiation Information Center, Research Institute for Radiation Biology and Medicine, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8553, Japan.
Yumiko
Y
Nitta
Kazuko
K
Yoshida
Naomi
N
Nakagata
Kohsaku
K
Nitta
Toshihide
T
Harada
Fumiko
F
Ishizaki
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000236:Adenoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000818:Animals; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011877:Radionuclide Imaging; D012097:Repressor Proteins / Q000235:genetics*; D015996:Survival Rate
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins