• Open Access

Congenital Hypothyroidism with Goiter in Tenterfield Terriers

Authors


  • 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.
  • 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

Corresponding author: J.C. Fyfe, DVM, PhD, 2209 Biomedical Physical Sciences, 567 Wilson Road, Michigan State University, East Lansing, MI 48824; e-mail: fyfe@cvm.msu.edu.

Abstract

Background

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.

Objectives

To describe the phenotype, thyroid histopathology, biochemistry, mode of inheritance, and causal mutation of CHG in Tenterfield Terriers.

Animals

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.

Methods

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.

Results

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.

Conclusions

The mutation underlying CHG in Tenterfield Terriers was identified, and a convenient carrier test made available for screening Tenterfield Terriers used for breeding.

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