Abstract
The variability in intestinal disease severity in patients with cystic fibrosis (CF) has been associated with the expression of secondary modifier genes. The locus containing these modifier genes in CF patients is syntenic with a modifier locus previously associated with survival in CF transmembrane conductance regulator–knockout mice. These previous studies showed that the proportion of CF mice that survive weaning (mildly affected mice) versus those that succumb to obstruction of the small intestine (severely affected) is related to their genetic background and the expression of modifier genes. In the present work, we show that the basal transepithelial chloride transport measured across jejuna obtained from mice of mixed genetic backgrounds segregates into two groups, some mice having low and others having high, near normal chloride transport. Further, we report that the segregation of mice with respect to intestinal chloride transport correlates with their predicted segregation on the basis of genotype at the “modifier locus.” These findings support the hypothesis that intestinal disease modification in CF mice correlates with improved chloride transport through non-CF transmembrane conductance regulator chloride channels.
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Abbreviations
- PD:
-
potential difference
- NPPB:
-
5-nitro-2-(3-phenylpropylamino)benzoic acid
- DIDS:
-
4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid
- CF:
-
cystic fibrosis
- CFTR:
-
cystic fibrosis transmembrane conductance regulator
- MI:
-
meconium ileus
- Wt:
-
wild type
- DPC:
-
N-diphenylanthranilic acid
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Acknowledgements
The authors thank Dr. Gerry Kent (HSC, Toronto) for providing the outbred CF mice and Dr. Mary Corey (HSC, Toronto) for providing consultation regarding our statistical analyses. We also thank Dr. L.C. Tsui for the use of inbred CF mice.
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Supported by grants from The Canadian Cystic Fibrosis Foundation (CCFF) and the MRC (Canada) to C.E.B. K.G. is a supported through a CCFF studentship.
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Gyömörey, K., Rozmahel, R. & Bear, C. Amelioration of Intestinal Disease Severity in Cystic Fibrosis Mice Is Associated with Improved Chloride Secretory Capacity. Pediatr Res 48, 731–734 (2000). https://doi.org/10.1203/00006450-200012000-00005
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DOI: https://doi.org/10.1203/00006450-200012000-00005
