Table 1. Effect of the genotype of (a) Atm and (b) Blm on intestinal tumor multiplicity.
The approximate fold-increase refers to Atm−/− or Blmm3/m3 compared to the other two classes. 129/S6 (129).Blmm3/+ mice were a gift from Allan Bradley (Baylor College of Medicine, Houston, TX); 129.Atm+/− mice were purchased from The Jackson Laboratory (Bar Harbor, ME); 129.Lig4+/− mice were a gift from Frederick Alt (Harvard University, Boston, MA). All mice were backcrossed to B6 for at least 11 (Atm), 10 (Blm), or 5 (Lig4) generations. Mouse husbandry and dissection were performed as previously described (Haigis et al., 2002). All mice were dissected between 3 and 5 months of age except for irradiated mice, which became moribund at 2 months. Whole-body IR was delivered using a Mark I 137 Cs irradiator, model 30 (J L Shepard & Assoc., San Fernando, CA), as previously described (Luongo and Dove, 1996). It was noted that Atm−/−;Apc1638N/+ and Blmm3/m3;Apc1638N/+ mice, but no other genotypic combination, developed numerous desmoid fibromas which were not enumerated.
| a | Atm+/+ | Atm+/− | Atm−/− | |||||
|---|---|---|---|---|---|---|---|---|
| Loc. | Tumor count, mean ± SD (incidence) | N | Tumor count, mean ± SD (incidence) | N | Tumor count, mean ± SD (incidence) | N | Fold Increase (95%CI‡) | |
| B6.ApcMin/+ | SI | 31 ± 7 | 47 | 35 ± 12 | 49 | 67 ± 10 | 17 | 2.0 (1.8–2.3)* |
| LI | 0.9 ± 1.5 (47%) | 1.1 ± 1.3 (47%) | 3.8 ± 3.7 (94%*) | 4.6 (2.2–9.3)* | ||||
| B6.ApcMin/+ +5.0Gy IR | SI | 280 ± 70 | 7 | 276 ± 54 | 12 | 267 ± 53 | 3 | 1.0 (0.7–1.3)† |
| LI | 7.7 ± 3.0 (100%) | 10 ± 7.5 (100%) | 22 ± 5.5 (100%†) | 2.4 (1.4–4.2)* | ||||
| B6.Apc1638N/+ | SI | 1.4 ± 1.1 | 13 | 1.5 ± 1.0 | 21 | 26 ± 9.4 | 20 | 16 (11–22)* |
| LI | 0 ± 0 (0%) | 0 ± 0 (0%) | 0.8 ± 0.8 (45%*) | N/A* | ||||
| b | Blm+/+ | Blmm3/+ | Blmm3/m3 | |||||
| Loc. | Tumor count, mean ± SD (incidence) | N | Tumor count, mean ± SD (incidence) | N | Tumor count, mean ± SD (incidence) | N | ~Fold-increase (95%CI‡) | |
| B6.ApcMin/+ | SI | 28 ± 12 | 9 | 25 ± 7 | 15 | 99 ± 16 | 4 | 3.8 (2.9–5.0)* |
| LI | 0.1 ± 0.3 (11%) | 0.4 ± 0.6 (33%) | 1.3 ± 0.5 (100%†) | 4.3 (1.8–21)* | ||||
| B6.Apc1638N/+ | SI | 1.8 ± 0.8 | 5 | 0.9 ± 1.1 | 8 | 6.2 ± 3.2 | 20 | 5.1 (2.8–10)* |
| LI | 0 ± 0 (0%) | 0 ± 0 (0%) | 0.1 ± 0.2 (5%†) | N/A† | ||||
p<0.05, Jonkheere-Terpstra Test or χ² test compared to controls
No significant difference
Bootstrap ratios comparing the homozygous knockouts to the combined heterozygotes and wildtypes; N/A, Not Applicable; SI, small intestine; LI, large intestine.