ABSTRACT
The study of Ataxia-telangiectasia (A-T) has benefited significantly from mouse models with knockout mutations for the Atm (A-T mutation) locus. While these models have proven useful for in vivo studies, cell cultures from Atm null embryos have been reported to grow poorly and then senesce. In this study, we initiated primary cultures from adult ears and kidneys of Atm homozygous mice and found that these cultures immortalized readily without loss of sensitivity to ionizing radiation and other Atm related cell cycle defects. A mutational analysis for loss of expression of an autosomal locus showed that ionizing radiation had a mutagenic effect. Interestingly, some spontaneous mutants exhibited a mutational pattern that is characteristic of oxidative mutagenesis. This result is consistent with chronic oxidative stress in Atm null cells. In total, the results demonstrate that permanent cell lines can be established from the tissues of adult mice homozygous for Atm and that these cell lines will exhibit expected and novel consequences of this deficiency.
Subject(s)
Ataxia Telangiectasia/genetics , Cell Line, Transformed , Oxidative Stress , Protein Serine-Threonine Kinases/genetics , Radiation, Ionizing , Animals , Ataxia Telangiectasia Mutated Proteins , Cell Cycle/radiation effects , Cell Cycle Proteins , Cell Survival/radiation effects , Chromosome Aberrations , DNA-Binding Proteins , Loss of Heterozygosity/radiation effects , Metaphase/radiation effects , Mice , Mice, Knockout , Mutagenesis , Mutation , Radiation Tolerance , Tumor Suppressor ProteinsABSTRACT
We tested 54 nonpsychotic first degree relatives of 23 schizophrenic probands and 18 control subjects matched for age and education on several neuropsychological tests. The tests were selected to assess overall intellectual ability or because previous work indicated that they are particularly sensitive measures of cognitive dysfunction in schizophrenic patients. The relatives of schizophrenic patients performed significantly worse than the control subjects on tests of verbal fluency and on Trailmaking, part B. Each of these tests contributed unique variance to the discrimination between groups. The groups did not differ significantly on the number of perseverative errors on the Wisconsin Card Sorting Test, Wechsler Adult Intelligence Scale-Revised block design or vocabulary, or Trailmaking, part A. Eight relatives who met DSM-III-R criteria for schizotypal personality disorder were more impaired than the remaining 46 relatives on letter fluency, but otherwise their performance was similar to that of nonschizotypal relatives. These data suggest that close relatives of schizophrenic patients may have subtle neuropsychological impairments that are not necessarily associated with clinical symptoms of schizophrenia spectrum disorders.