Table 1. Atm loss exacerbates Tdp1 deficiency.
Genetic analysis shows synthetic lethality after coincident loss of Tdp1 and Atm. Compound mutants involving DNA double strand break repair (Lig4 or Prkdc) or MRN (Mre11ATLD/ATLD) deficiency do not affect the expected rate of generation of compound mutant mice. Mouse genetic inheritance ratios were calculated using standard rules for Mendelian genetic inheritance: “Expected” and “Observed” ratios were calculated based upon parental genotypes and the number of live-born mice.
| Genotype | Expected N= | Observed N= | |
|---|---|---|---|
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| Atm−/− × Tdp1−/− | Control | 969 | 1083 |
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| Mutant | 125 | 11 | |
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| AtmNes-cre × Tdp1−/− | Control | 360 | 474 |
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| Mutant | 120 | 6 | |
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| Mre11ATLD/ATLD × Tdp1−/− | Control | 105 | 108 |
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| Mutant | 15 | 12 | |
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| Lig4Nes-cre × Tdp1−/− | Control | 284 | 283 |
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| Mutant | 9 | 10 | |
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| Prkdc−/− × Tdp1−/− | Control | 166 | 166 |
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| Mutant | 9 | 10 | |