This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takabayashi, S. Articles by Katoh, H. Search for Related Content PubMed PubMed Citation Articles by Takabayashi, S. Articles by Katoh, H.

A Novel Hypothyroid Dwarfism Due to the Missense Mutation Arg479Cys of the Thyroid Peroxidase Gene in the Mouse

Institute for Experimental Animals (S.T., E.Y., H.K.), and Department of Parasitology (T.S.), Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan; and Clinical Laboratory (K.U.), University of Miyazaki Hospital, and Department of Rheumatology, Infectious Diseases and Laboratory Medicine, Faculty of Medicine (A.O.), University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki 889-1692, Japan

Address all correspondence and requests for reprints to: Hideki Katoh, Institute for Experimental Animals, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan. E-mail: Hideki-k{at}hama-med.ac.jp.

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.

This article has been cited by other articles:

				K. Kano, C. Marin de Evsikova, J. Young, C. Wnek, T. P. Maddatu, P. M. Nishina, and J. K. Naggert A Novel Dwarfism with Gonadal Dysfunction Due to Loss-of-Function Allele of the Collagen Receptor Gene, Ddr2, in the Mouse Mol. Endocrinol., August 1, 2008; 22(8): 1866 - 1880. [Abstract] [Full Text] [PDF]

				K. R. Johnson, C. C. Marden, P. Ward-Bailey, L. H. Gagnon, R. T. Bronson, and L. R. Donahue Congenital Hypothyroidism, Dwarfism, and Hearing Impairment Caused by a Missense Mutation in the Mouse Dual Oxidase 2 Gene, Duox2 Mol. Endocrinol., July 1, 2007; 21(7): 1593 - 1602. [Abstract] [Full Text] [PDF]