27. Absence of Linkage between Radiosensitivity and the Predisposing Atp7b Gene Mutation for Heritable Hepatitis in the LEC Rat

Toshiaki Ogiu, Mayumi Nishmmura, Fumiaki Watanabe, Hideki Ukai, Hiroko Ishii-Ohba, Yoshiya Shimada, Hideo Tsuji, Junko Sakurai and Okio Hino

Keywords: LEC rats, radiosensitivity, X-rays, Atp7b gene, linkage analysis

The LEC rat is known to be a mutant strain that spontaneously develops heritable hepatitis due to copper accumulation, caused by mutation of the copper transporting ATPase gene (Atp7b) . Immunodeficiency and radiosensitivity have also been observed. Hayashiet al. extensively examined the radiosensitivity of the LEC rat and concluded that its hypersensitivity is controlled by a single autosomal gene. Furthermore, they suggested the possibility that it correlates to copper accumulation due to the Atp7b gene mutatton, because ionizing radiation-induced hydroxyl radicals might act in concert with copper-induced hydroxyl radicals. In the present experiment, we analyzed linkage between radiosensitivity and the mutatnon responsible for LEC hepatitis in F₁ animals of cross with the F344 rat (Table 4). Our results clearly demonstrated an absence of any significant association. In addition, partial dominance for radiosensitivity was o bserved and radiosensitive (F₁ X LEC) backcross rats were twice as numerous as their radioresistant counterparts, suggesting the possibility of control by two or more recessnve genes.

Table 4. Number of [(F344xLEC) F1xLEC] backcross Rats with Each Combination of Radiosensitivity and Atp7b Genotype

^aRadiosensitivity was determined on the basis of the mortality at 30 days after whole body irradiation with 4.0 or 4.5Gy of X-rays.
^bGenotype was determined by Southern blot analysis. LEC means LEC genotype and F344 genotype.