Sites: The local veterinarian (RD) contributed clinical assessment, sample collection, and contacts with participating breeders. Enzymology, histopathology, and molecular investigations were performed at the College of Veterinary Medicine, Michigan State University, East Lansing, MI.
Congenital Hypothyroidism with Goiter in Tenterfield Terriers
Article first published online: 1 NOV 2012
Copyright © 2012 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 26, Issue 6, pages 1350–1357, November/December 2012
How to Cite
Dodgson, S.E., Day, R. and Fyfe, J.C. (2012), Congenital Hypothyroidism with Goiter in Tenterfield Terriers. Journal of Veterinary Internal Medicine, 26: 1350–1357. doi: 10.1111/j.1939-1676.2012.01015.x
Meeting presentation: These data were presented as a poster in preliminary form at the 5th International Conference: Advances in Canine and Feline Genomics and Inherited Diseases, Baltimore, MD, September 22–25, 2010
- Issue published online: 20 NOV 2012
- Article first published online: 1 NOV 2012
- Manuscript Accepted: 5 SEP 2012
- Manuscript Revised: 15 AUG 2012
- Manuscript Received: 20 APR 2012
- Peabody Award
- Carrier test;
- DNA sequence;
- Enzyme assay;
- Thyroid peroxidase;
- Western blot
A cluster of cases of congenital hypothyroidism with goiter (CHG) in Tenterfield Terriers was identified and hypothesized to be dyshormonogenesis of genetic etiology with autosomal recessive inheritance.
To describe the phenotype, thyroid histopathology, biochemistry, mode of inheritance, and causal mutation of CHG in Tenterfield Terriers.
Thyroid tissue from 1 CHG-affected Tenterfield Terriers, 2 affected Toy Fox Terriers, and 7 normal control dogs. Genomic DNA from blood or buccal brushings of 114 additional Tenterfield Terriers.
Biochemical and genetic segregation analysis of functional gene candidates in a Tenterfield Terrier kindred. Thyroid peroxidase (TPO) iodide oxidation activity was measured, and TPO protein and SDS-resistant thyroglobulin aggregation were assessed on western blots. TPO cDNA was amplified from thyroid RNA and sequenced. Exons and flanking splice sites were amplified from genomic DNA and sequenced. Variant TPO allele segregation was assessed by restriction enzyme digestion of PCR products.
Thyroid from an affected pup had lesions consistent with dyshormonogenesis. TPO activity was absent, but normal sized immunocrossreactive TPO protein was present. Affected dog cDNA and genomic sequences revealed a homozygous TPO missense mutation in exon 9 (R593W) that was heterozygous in all obligate carriers and in 31% of other clinically normal Tenterfield Terriers.
The mutation underlying CHG in Tenterfield Terriers was identified, and a convenient carrier test made available for screening Tenterfield Terriers used for breeding.