Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder

Mucocele formation in dogs is a unique and enigmatic muco-obstructive disease of the gallbladder caused by amassment of abnormal mucus that bears striking pathological similarity to cystic fibrosis. We investigated the role of CFTR in the pathogenesis of this disease. The location and frequency of disease-associated variants in the coding region of CFTR was compared using whole genome sequence data from 2,642 dogs representing breeds at low-risk, high-risk, or with confirmed disease. Expression, localization, and ion transport activity of CFTR was quantified in control and mucocele gallbladders by NanoString, Western blotting, immunofluorescence imaging, and studies in Ussing chambers. Our results establish significant loss of CFTR-dependent anion secretion by mucocele gallbladder mucosa. A significantly lower quantity of CFTR protein was demonstrated relative to E-cadherin in mucocele compared to control gallbladder mucosa. Immunofluorescence identified CFTR along the apical membrane o..., We used the Whole Animal Genome Sequencing (WAGS) pipeline to identify short nucleotide variants in a dataset of 2,642 dogs encompassing both private and public resources including 1,971 genomes from the Dog10K project. Briefly, the WAGS pipeline used Burrows-Wheeler Alignment tool-MEM to map paired-end reads to the UU_Cfam_GSD_1.0 reference genome. Variant calling was executed with Genome Analysis Toolkit (GATK4), and Ensembl’s Variant Effect Predictor (VEP, RRID:SCR_007931) predicted variant annotations and consequences. From the resulting VEP-processed VCF file, we extracted CFTR genic variants plus variants within 1Kb of the flanking sequence that passed filters. Subsequently, non-reference allele frequencies were calculated for each variant within the control, risk, and affected dog groups. , , # Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder.

[https://doi.org/10.5061/dryad.2rbnzs7xq](https://doi.org/10.5061/dryad.2rbnzs7xq)

This dataset includes supplementary materials for the manuscript entitled *Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder*.

## Description of the data and file structure

**Supplemental Figure S1** illustrates sample procurement and appearance of gallbladder from each of 9 dogs having mucosal RNA extracted for targeted gene expression analysis. Samples of lumen mucosa were obtained by excision from regions devoid of mucus or from which mucus could be gently removed. During sampling (panel A) and after removal of sample (panel B). Remaining panels show each of 9 individual mucocele gallbladders used for mucosal RNA sample collection. Pictures are immediately post-cholecystectomy followed by opening of the gallbladder to expose the lumen.

**Supplemental Table S1...