01674-A: Molecular Basis of Congenital Hypothyroidism with Goiter in Spanish Water Dogs

Grant Status: Closed

Grant Amount: $12,955
John C. Fyfe, DVM, PhD; Michigan State University
July 1, 2011 - June 30, 2012

Sponsor(s): Afghan Hound Club of America, Keeshond Anonymous Fund

Breed(s): Spanish Water Dog
Research Program Area: Endocrinology
Donate to Support this Research Program Area

Project Summary

Recently, congenital hypothyroidism with goiter (CHG) occurred in Spanish Water Dogs (SWD), a breed that was recognized by the AKC Foundation Stock Service in 2005 and approved for a variety of performance competitions in 2008. Hormones produced by the thyroid gland are crucially important for the health and development of dogs. Affected puppies exhibited mental dullness, dwarfism, enlarged thyroid glands, failure to suckle, and early death unless treated aggressively with thyroid hormone replacement. Even so, early diagnosis and treatment are only partially effective. The pattern of disease occurrence suggested autosomal recessive inheritance, and hormone testing of affected dogs indicated a problem of the thyroid gland itself. In collaboration with SWD breeders we undertook to determine the underlying mutation causing SWD congenital hypothyroidism and to provide a carrier test to be used to prevent future matings between carriers, while not selecting against desirable traits of the breed. SWD owners provided pedigree information, cheek brush samples for DNA isolation from affected, obligate carrier, and more distantly related dogs, and a piece of frozen affected dog thyroid tissue left over from a diagnostic biopsy. We used a "functional candidate gene" approach, first determining the enzymatic activity and presence of thyroid peroxidase (TPO) protein in affected and normal dog thyroids. TPO is crucial for thyroid hormone synthesis and is mutated in several cases of dog and human CHG. Neither TPO activity nor protein was detectable in the affected dog thyroid. Subsequently we amplified and sequenced TPO cDNA from the affected and normal dog thyroids. We determined that the affected dog was homozygous for a single guanine (G) insertion in a canid-specific portion of the gene that was incompatible with expression of the enzyme and, therefore, explained the disease. Obligate carriers in the SWD pedigree were heterozygous, as were 19 of 40 other clinically normal SWD tested. The disease mutation is the basis of a genetic carrier test conducted on cheek brush samples now offered to the public by the Laboratory of Comparative Medical Genetics at Michigan State University. Indications are that at least 2 dogs carrying the disease mutation have been imported from Europe and that carriers are distributed in a number of kennels. For more information on the test and/or to request a sampling kit, email fyfe@msu.edu .


Fyfe, J. C., Lynch, M., Olsen, J., & Lou?r, E. (2013). A thyroid peroxidase (TPO) mutation in dogs reveals a canid-specific gene structure. Mammalian Genome, 24(3–4), 127–133. https://doi.org/10.1007/s00335-012-9442-y
Major, S., Pettigrew, R. W., & Fyfe, J. C. (2015). Molecular Genetic Characterization of Thyroid Dyshormonogenesis in a French Bulldog. Journal of Veterinary Internal Medicine, 29(6), 1534–1540. https://doi.org/10.1111/jvim.13651

Help Future Generations of Dogs

Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases.

Learn How to Help

Connect With Us:
Get Canine Health News:
Please leave this field empty
American Kennel Club Canine Health Foundation, Inc

8051 Arco Corporate Dr.
Suite 300
Raleigh, NC 27617

Tax ID# 13-3813813

   2020 GuideStar logo

© 2020 AKC Canine Health Foundation | Privacy Policy | Site Map

Site by Blackbaud, Inc.

Powered by Blackbaud
nonprofit software