Naturally occurring mutations in the canine CFTR gene

Area of Science:

• Genetics
• Veterinary Medicine
• Molecular Biology

Background:

• Cystic fibrosis (CF) is a genetic disorder in humans caused by mutations in the CFTR gene.
• No naturally occurring CF-causing CFTR mutations have been identified in nonhuman animals.
• Domestic dogs exhibit conditions similar to human CF, such as bronchiectasis and pancreatitis.

Purpose of the Study:

• To investigate the prevalence of CFTR mutations in domestic dogs.
• To determine if dogs with pancreatitis or bronchiectasis have a higher incidence of CFTR mutations compared to the general dog population.

Main Methods:

• Screened canine CFTR genes in 400 dogs using Temporal Temperature-Gradient Gel Electrophoresis (TTGE).
• Included 203 dogs with pancreatitis, 23 with bronchiectasis, and 174 general clinic dogs.
• Identified and characterized four CFTR missense mutations.

Main Results:

• Identified four CFTR missense mutations in 28 out of 400 dogs.
• Found no significant difference in mutation frequency between dogs with pancreatitis, bronchiectasis, and the general population.
• Characterized mutations R1456W (analogous to human R1453W) and R812W (disrupting a conserved PKA site).

Conclusions:

• Naturally occurring CFTR mutations are relatively common in domestic dogs.
• TTGE is an effective method for detecting canine CFTR mutations.
• The presence of these mutations did not correlate with specific clinical conditions like pancreatitis or bronchiectasis in this study.