Molecular and Genetic Characterization of a Radiation-Induced Structural Rearrangement in Mouse Chromosome 2 Causing Mutations at the Limb Deformity and Agouti Loci

• Published in: Proceedings of the National Academy of Sciences - PNAS 1990-04, Vol.87 (7), p.2588-2592
• Main Authors: Woychik, R. P., Generoso, W. M., Russell, L. B., Cain, K. T., Cacheiro, N. L. A., Bultman, S. J., Selby, P. B., Dickinson, M. E., Hogan, B. L. M., Rutledge, J. C.
• Format: Article
• Language: English
• Subjects: 560152 - Radiation Effects on Animals- Animals; Abnormalities, Radiation-Induced - genetics; Alleles; ANIMALS; Biological and medical sciences; BIOLOGICAL EFFECTS; BIOLOGICAL RADIATION EFFECTS; CHROMOSOMAL ABERRATIONS; Chromosome Aberrations; Chromosome Banding; Chromosome Disorders; CHROMOSOMES; Chromosomes - radiation effects; CLONING; Cloning, Molecular; Crosses, Genetic; Cytogenetics; DNA; DNA probes; ELECTROMAGNETIC RADIATION; Female; Fundamental and applied biological sciences. Psychology; GAMMA RADIATION; Gamma Rays; GENE MUTATIONS; Genes; GENETIC EFFECTS; Genetic loci; Genetic mutation; GENETIC RADIATION EFFECTS; Genetics of eukaryotes. Biological and molecular evolution; Homozygote; IONIZING RADIATIONS; KARYOTYPE; Karyotyping; Kidneys; Male; MAMMALS; Medical genetics; MICE; Mice, Inbred Strains; MOLECULAR BIOLOGY; Mutation; MUTATIONS; RADIATION EFFECTS; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; RADIATIONS; RADIOINDUCTION; Restriction Mapping; RNA; RODENTS; STRAND BREAKS; Vertebrata; VERTEBRATES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.7.2588

Molecular characterization of mutations in the mouse, particularly those involving agent-induced major structural alterations, is proving to be useful for correlating the structure and expression of individual genes with their function in the whole organism. Here we present the characterization of a radiation-induced mutation that simultaneously generated distinct alleles of both the limb deformity (ld) and agouti (a) loci, two developmentally important regions of chromosome 2 normally separated by 20 centimorgans. Cytogenetic analysis revealed that an interstitial segment of chromosome 17 (17B-17C; or, possibly, 17A2-17B) had been translocated into the distal end of chromosome 2, resulting in a smaller-than-normal chromosome 17 (designated 17del) and a larger form of chromosome 2 (designated 217). Additionally, a large interstitial segment of the 217chromosome, immediately adjacent and proximal to the insertion site, did not match bands 2E4-2H1 at corresponding positions on a normal chromosome 2. Molecular analysis detected a DNA rearrangement in which a portion of the ld locus was joined to sequences normally tightly linked to the a locus. This result, along with the genetic and cytogenetic data, suggests that the alleles of ld and a in this radiation-induced mutation, designated ldIn2and ajIn2, were associated with DNA breaks caused by an inversion of an interstitial segment in the 217chromosome.