title: Assessment of the flexed-tail mouse as a possible model for Fanconi anemia: analysis of mitomycin C-induced micronuclei.
abstract: Fanconi anemia (FA) is a rare, autosomal recessive disorder characterized by elevated frequencies of chromosome aberrations, hypersensitivity to DNA cross-linking agents and predisposition to cancer. At least 5 complementation groups (FA-A to FA-E) underlie FA and the gene defective in FA-C (FAC) has been cloned. The mouse orthologue, Fac, maps in close proximity to the f locus, on chromosome 13, which codes for the flexed-tail mouse phenotype, raising the possibility that f and Fac are synonymous. If this were the case flexed-tail mice could be used as mouse models for FA-C to help determine the basic defect and to evaluate clinical intervention and gene therapy. To further characterize the flexed-tail mouse, the frequency of micronuclei (a measure of chromosomal aberrations) induced by mitomycin C (MMC), an alkylating and DNA cross-linking agent, was analyzed in peripheral blood and bone marrow erythrocytes. Although a higher spontaneous micronucleus frequency was seen in flexed tail mice in comparison to wild-type mice, the sensitivity to MMC was not elevated. This result suggests that f and Fac are different genes and that the flexed-tail mouse is not a model for FA-C.
authors.affiliation: Department of Biology, York University, Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Urlando
authors.forename: F
authors.initials: F
authors.lastname: Krasnoshtein
authors.forename: J A
authors.initials: JA
authors.lastname: Heddle
authors.forename: M
authors.initials: M
authors.lastname: Buchwald
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005199:Fanconi Anemia / Q000235:genetics*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D016685:Mitomycin / Q000633:toxicity*
chemical_list: D000903:Antibiotics, Antineoplastic; D016685:Mitomycin