CF mice on the mixed background have improved survival
As reported by others [34], the expected number of Cftr null mice on the B6 background that survived to weaning was significantly less than that expected from Mendelian genetics (Tables 1 and 2). The degree of significance was greater for male mice (Tables 1 and 2). In contrast, on the mixed background, the distribution of genotypes of female offspring was not significantly different from the expected (Tables 1). For male mice on the mixed background, the P-value was less significant but still different compared to the B6 males (Table 2). These data indicate that the mixed background is associated with increased survival of CF mice.
Table 1  Distribution of Cftr genotypes in female offspring from breeding Cftr heterozygotes on the B6 and mixed backgrounds.
B6 Background  Mixed Background
Cftr  Observed  Expected  Observed  Expected
+/+  207  175  57  47
+/-  371  350  88  94
-/-  122  175  42  47
P  0.00001 (0.04533)*   0.21724
Statistical analysis was by Chi-square. (*) P-value if the sample size for the B6 mice is adjusted to be equal to that of the mixed background mice, assuming the same distribution of genotypes.
Table 2  Distribution of Cftr genotypes in male offspring from breeding Cftr heterozygotes on the B6 and mixed backgrounds.
B6 Background  Mixed Background
Cftr  Observed  Expected  Observed  Expected
+/+  240  201  57  52
+/-  431  403  115  104
-/-  134  201  36  52
P  <0.00001 (0.01612)*   0.03749
Statistical analysis was by Chi-square. (*) P-value if the sample size for the B6 mice is adjusted to be equal to that of the mixed background mice, assuming the same distribution of genotypes. The major cause of death in CF mice is intestinal obstruction, and intestinal obstruction is worsened when the mice are fed standard solid mouse chow [35]. Since the CF mice on the mixed background had better weight gain than on the B6 background and less mucus accumulation in the small intestine, their ability to survive on solid chow was tested. Mice were maintained on the liquid diet until 8 weeks of age, and then switched to solid chow for up to eight weeks. As shown in Fig. 4, wild type mice had 100% survival on chow, as expected. The majority of CF mice on the B6 background died within 2–3 weeks on solid chow, with about 60% mortality over the 8 week period. In contrast, only 22% of the CF mice on the mixed background died (Fig. 4).
Figure 4  Effect of genetic background on CF mouse survival on solid chow. Mice were maintained on the liquid diet (Peptamen) until 8 weeks of age, at which time they were fed standard solid mouse chow for up to 8 additional weeks. Deaths were recorded as they occurred and mice in obvious distress were sacrificed and 'death' recorded as the subsequent day. By log-rank test, CF mice on the mixed background had significantly earlier death compared to wild type (P = 0.035), and significantly later death than CF mice on the B6 background (P = 0.025). CF mice on the B6 background also died significantly earlier than wild type (P < 0.0005).