Spontaneously immortalized cell lines obtained from adult Atm null mice retain sensitivity to ionizing radiation and exhibit a mutational pattern suggestive of oxidative stress.
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.
Gage
B M
BM
Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland, Oregon, OR 97201, USA.
Alroy
D
D
Shin
C Y
CY
Ponomareva
O N
ON
Dhar
S
S
Sharma
G G
GG
Pandita
T K
TK
Thayer
M J
MJ
Turker
M S
MS
D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000528:radiation effects; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000528:radiation effects; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins; D019656:Loss of Heterozygosity / Q000528:radiation effects; D008677:Metaphase / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis; D009154:Mutation; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases