PMC:1166548 / 10736-14406 JSONTXT

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In contrast, the intestine of CF mice on the B6 genetic background exhibited greatly dilated crypts filled with PAS-reactive mucus (Fig. 3B). CF mice on the mixed background had less mucus accumulation than CF mice on the B6 background (Fig. 3D-F). The amount of mucus in CF mice on the mixed background was variable from mouse to mouse. In some mice (Fig. 3D), only occasional crypts had accumulated mucus and the crypt lumina were not very dilated. In some mice there was more mucus in the crypts (Fig. 3E), while others had moderate mucus accumulation (Fig. 3F). A total of six CF mice on the mixed background were examined histologically, and three had little mucus, one had some mucus, and two had moderate amounts of mucus. Despite the variability, all the CF mice on the mixed background had less crypt dilation and less mucus accumulation compared to CF mice on the B6 background.\nFigure 3 Histological appearance of the small intestine of wild type and CF mice on the different genetic backgrounds. Tissue was paraffin embedded and stained with PAS for neutral mucins. The sections are from the middle portion of the small intestine (A) Wild type on the B6 background. (B) CF on the B6 background. (C) Wild type on the mixed background. (D-F) CF on the mixed background. (A, C) In the wild type tissue from both backgrounds, the crypts are small and have narrow lumina (arrows). (B) In the CF tissue on the B6 background, the crypt lumina are greatly dilated and filled with PAS-reactive mucus (arrows). In some CF mice on the mixed background, the crypts are not apparently different than wild type (D), and the crypts are normal appearing (arrows). Some CF mice on the mixed background had mildly affected crypts (E), while others had greater crypt dilation and mucus accumulation (F). Overall, the CF mice on the mixed background were less severely affected compared to those on the B6 background. Thus, it appears that whatever the nature of the genetic differences between the two background strains, they affect secretion and accumulation of mucus in the CF small intestine. To determine if the difference could be accounted for by altered mucin gene expression, quantitative RT-PCR was used to measure mRNA expression of the intestinal goblet cell mucin gene, Muc2. In wild type intestine, B6 mice had 0.079 +/- 0.024 copies of Muc2/GAPDH (n = 8), and on the mixed background the level was 0.077 +/- 0.012 (n = 11). CF mice on the B6 background had 0.059 +/- 0.024 copies of Muc2 mRNA per GAPDH (n = 11), and on the mixed background the level was 0.056 +/- 0.010 (n = 11). Despite the increased mucus accumulation in CF, there is a slight decrease in Muc2 mRNA in the CF small intestine (P \u003c 0.0001), as previously reported [33]. However, the milder CF phenotype on the mixed background, which includes less mucus accumulation, does not involve decreased mucin gene 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