PMC:1166548 / 14408-17486 JSONTXT

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These data indicate that the mixed background is associated with increased survival of CF mice.\nTable 1 Distribution of Cftr genotypes in female offspring from breeding Cftr heterozygotes on the B6 and mixed backgrounds.\nB6 Background Mixed Background\nCftr Observed Expected Observed Expected\n+/+ 207 175 57 47\n+/- 371 350 88 94\n-/- 122 175 42 47\nP 0.00001 (0.04533)* 0.21724\nStatistical 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.\nTable 2 Distribution of Cftr genotypes in male offspring from breeding Cftr heterozygotes on the B6 and mixed backgrounds.\nB6 Background Mixed Background\nCftr Observed Expected Observed Expected\n+/+ 240 201 57 52\n+/- 431 403 115 104\n-/- 134 201 36 52\nP \u003c0.00001 (0.01612)* 0.03749\nStatistical 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).\nFigure 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 \u003c 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