Phenotypic correction of ataxia-telangiectasia cellular defect by exogenously introduced human or mouse subchromosomal fragments.
A human-mouse hybrid containing a human 11q22-23 fragment including the ATM locus was used to examine its capability to correct the cellular defect of ataxia-telangiectasia (A-T). Examination of 21 A-T-derived hybrids indicated that the acquired radioresistance was observed in the clones where the 11q22-23 fragment was transferred intact, but not in those where donor-derived 11q segment was lost. In one exceptional clone, the ATM locus was deleted from the transferred fragment, while it was still partially radioresistant. This partially radioresistant clone was found to include the mouse-derived fragment containing the Atm gene, the mouse homologue of human ATM gene. Similar association of partial radioresistance with the presence of mouse Atm gene was observed in three additional hybrids. The results indicate that the cellular A-T defect can be corrected by the mouse subchromosomal fragment containing the Atm gene as well as by the human 11q22-23 fragment containing the ATM gene, but apparently to a lesser extent in the former.
Ejima
Y
Y
Radiation Biology Center, Kyoto University, Japan.
Sasaki
M S
MS
D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000628:therapy*; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics / Q000648:ultrastructure; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D006822:Hybrid Cells; D051379:Mice; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D013045:Species Specificity; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases