A novel hypothyroid dwarfism due to the missense mutation Arg479Cys of the thyroid peroxidase gene in the mouse.

Abstract

Recently, we found a novel dwarf mutation in an ICR closed colony. This mutation was governed by a single autosomal recessive gene. In novel dwarf mice, plasma levels of the thyroid hormones, T3 and T4, were reduced; however, TSH was elevated. Their thyroid glands showed a diffuse goiter exhibiting colloid deficiency and abnormal follicle epithelium. The dwarfism was improved by adding thyroid hormone in the diet. Gene mapping revealed that the dwarf mutation was closely linked to the thyroid peroxidase (Tpo) gene on chromosome 12. Sequencing of the Tpo gene of the dwarf mice demonstrated a C to T substitution at position 1508 causing an amino acid change from arginine (Arg) to cysteine (Cys) at codon 479 (Arg479Cys). Western blotting revealed that TPO protein of the dwarf mice was detected in a microsomal fraction of thyroid tissue, but peroxidase activity was not detected. These findings suggested that the dwarf mutation caused a primary congenital hypothyroidism by TPO deficiency, resulting in a defect of thyroid hormone synthesis.

• Authors: Shuji Takabayashi, Kazumi Umeki, Etsuko Yamamoto, Tohru Suzuki, Akihiko Okayama, Hideki Katoh
• Journal: Molecular endocrinology (Baltimore, Md.) (Mol Endocrinol) Vol. 20 Issue 10 Pg. 2584-90 (Oct 2006) ISSN: 0888-8809 [Print] United States
• PMID: 16762971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Thyroid Hormones
• Thyrotropin
• Iodide Peroxidase

Topics

• Animals
• Base Sequence
• Blotting, Western
• Chromosome Mapping
• Crosses, Genetic
• Dwarfism (drug therapy, genetics, pathology, veterinary)
• Genes, Recessive (genetics)
• Hypothyroidism (drug therapy, genetics, pathology, veterinary)
• Iodide Peroxidase (genetics)
• Mice
• Microsatellite Repeats (genetics)
• Mutation, Missense (genetics)
• Phenotype
• Rodent Diseases (drug therapy, genetics, pathology)
• Sequence Analysis, DNA
• Thyroid Hormones (blood, therapeutic use)
• Thyrotropin (blood)