title: Absence of linkage between radiosensitivity and the predisposing atp7b gene mutation for heritable hepatitis in the LEC rat.
abstract: 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. Hayashi et 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 mutation, 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 mutation responsible for hepatitis in F(1) animals of a cross with the F344 rat. Our results clearly demonstrated an absence of any significant association. In addition, partial dominance for radiosensitivity was observed, and radiosensitive (F(1) x LEC) backcross rats were twice as numerous as their radioresistant counterparts, suggesting the possibility of control by two or more recessive genes.
authors.affiliation: Low Dose Radiation Risk and Carcinogenesis Research Group, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ogiu
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: F
authors.initials: F
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Ukai
authors.forename: H
authors.initials: H
authors.lastname: Ishii-Ohba
authors.forename: Y
authors.initials: Y
authors.lastname: Shimada
authors.forename: H
authors.initials: H
authors.lastname: Tsuji
authors.forename: J
authors.initials: J
authors.lastname: Sakurai
authors.forename: O
authors.initials: O
authors.lastname: Hino
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D000073840:Copper-Transporting ATPases; D004307:Dose-Response Relationship, Radiation; D005260:Female; D008040:Genetic Linkage; D006505:Hepatitis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D020332:Rats, Inbred LEC
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases