Senescence-Accelerated Mouse (SAM) strains have a spontaneous mutation in the Abcb1a gene. 2008

Guohong Zhang, and Beiru Zhang, and Xiaoying Fu, and Hiroshi Tomozawa, and Kiyoshi Matsumoto, and Keiichi Higuchi, and Masayuki Mori
Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan.

Senescence-Accelerated Mouse (SAM) strains are used as animal models for gerontological research. Here, we report that the SAMR1 strain, which shows a high sensitivity to toxicity of the parasiticide ivermectin, has a spontaneous retroviral insertional mutation in the ATP-binding cassette, sub-family B (MDR/TAP), member 1A (Abcb1a) gene. This mutation is identical to that found in Crl:CF1-Abcb1a mice, which are also highly sensitive to ivermectin due to the mutation. The mutant Abcb1a allele was found in SAMR4, SAMR5, SAMP1, SAMP6, SAMP7, and SAMP9, but not in SAMP3, SAMP8, SAMP10, SAMP11, and other outbred and inbred strains, including 129/SvJ strains. These results impart both caution and promise in the use of SAM strains in studies of biological processes in which P-glycoprotein participates.

UI MeSH Term Description Entries
D007559 Ivermectin A mixture of mostly avermectin H2B1a (RN 71827-03-7) with some avermectin H2B1b (RN 70209-81-3), which are macrolides from STREPTOMYCES avermitilis. It binds glutamate-gated chloride channel to cause increased permeability and hyperpolarization of nerve and muscle cells. It also interacts with other CHLORIDE CHANNELS. It is a broad spectrum antiparasitic that is active against microfilariae of ONCHOCERCA VOLVULUS but not the adult form. Eqvalan,Ivomec,MK-933,Mectizan,Stromectol,MK 933,MK933
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000977 Antiparasitic Agents Drugs used to treat or prevent parasitic infections. Antiparasitic,Antiparasitic Agent,Antiparasitic Drug,Parasiticide,Parasiticides,Antiparasitic Drugs,Antiparasitics,Agent, Antiparasitic,Agents, Antiparasitic,Drug, Antiparasitic,Drugs, Antiparasitic
D012376 Rodent Diseases Diseases of rodents of the order RODENTIA. This term includes diseases of Sciuridae (squirrels), Geomyidae (gophers), Heteromyidae (pouched mice), Castoridae (beavers), Cricetidae (rats and mice), Muridae (Old World rats and mice), Erethizontidae (porcupines), and Caviidae (guinea pigs). Disease, Rodent,Diseases, Rodent,Rodent Disease
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D019588 Aging, Premature Changes in the organism associated with senescence, occurring at an accelerated rate. Premature Aging

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