Autosomal mutation in somatic cells of the mouse.
Tumor suppressor genes are located on autosomal chromosomes. Therefore, an understanding of how cancer-related mutations occur in somatic cells requires a detailed understanding of spontaneous and induced autosomal mutagenesis. This review will present recent advances in the study of how autosomal mutations form in somatic cells by focusing on the mouse Aprt and Tk model systems that have been developed to examine the formation of autosomal mutations in vivo. These loci can detect the entire spectrum of mutations known to inactivate tumor suppressor genes. Studies with these models have provided novel information on the frequencies and types of spontaneous autosomal mutations that occur in different cell types. They also show great promise for the screening of genotoxic effects resulting from environmental exposures and for the study of mutation when DNA repair pathways are compromised. Continued use of the mouse Aprt and Tk models will have a significant impact on our understanding of some of the earliest steps in the conversion of normal cells to those with malignant phenotypes.
Turker
Mitchell S
MS
Center for Research on Occupational and Environmental Toxicology and Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR 97239, USA. turkerm@ohsu.edu
D048868:Adaptor Proteins, Signal Transducing; D000228:Adenine Phosphoribosyltransferase / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D005796:Genes / Q000187:drug effects / Q000528:radiation effects; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D019656:Loss of Heterozygosity; D051379:Mice / Q000235:genetics*; D008817:Mice, Mutant Strains; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000009:adverse effects; D009154:Mutation; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics; D009687:Nuclear Proteins; D009928:Organ Specificity; D010641:Phenotype; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; C501485:Mlh1 protein, mouse; D009153:Mutagens; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C501002:Xpc protein, mouse; D000228:Adenine Phosphoribosyltransferase; D013937:Thymidine Kinase; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D000251:Adenosine Triphosphatases; C499533:Pms2 protein, mouse; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes