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Gene Review

Dio3  -  deiodinase, iodothyronine type III

Mus musculus

Synonyms: 5DIII, DIOIII, Type 3 DI, Type III iodothyronine deiodinase, Type-III 5'-deiodinase
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High impact information on Dio3

  • D3 inactivates thyroxine (T4) and T3 by 5-deiodination, and the gene for this enzyme, Dio3, lies in the imprinted domain on human chromosome 14q32/distal mouse chromosome 12 [1].
  • These results demonstrate that disruption of the imprinting status of Dio3 results in abnormal thyroid hormone levels and may contribute to the phenotypic abnormalities in UPD12 mice and UPD14 humans [1].
  • Northern analysis of mRNA from E15 fetuses showed that the Dio3 mRNA transcripts generated from the paternal allele were at least 5 times more abundant than the transcripts originated from the maternal allele [2].
  • We conclude that the Dio3 gene is subject to genomic imprinting and preferentially expressed from the paternal allele in the mouse fetus [2].
  • We compared Dio3 gene expression in fetuses that were either wild type or heterozygous (+/-Dio3) for the mutation [2].

Biological context of Dio3

  • The imprinted Dlk1-Dio3 region on mouse chromosome 12 contains six imprinted genes and a number of maternally expressed snoRNAs and miRNAs [3].
  • These results are consistent with the observed phenotype in Gtl2lacZ mice, because at least two Pegs(Peg9/Dlk1 and Dio3) have growth-promoting effects [4].
  • To gain further insights into the structure, functional role, and regulation of this enzyme, we screened a mouse liver genomic library with a rat D3 complementary DNA probe and isolated a 12-kb clone coding for the Dio3 [5].
  • The cell-specific serum response of the Dio3 promoter and the identified enhancer may play critical roles in the regulation of gene expression at this imprinted locus [6].
  • In addition, we identified a conserved enhancer located 3' of the gene containing putative AP-1 and serum response elements, and that further increases the serum responsiveness of the Dio3 promoter in a cell-specific manner [6].

Anatomical context of Dio3

  • Both mouse and human Dio3 promoters are markedly responsive to serum and, to a lesser extent, to phorbol esters and fibroblast growth factor, but only in a cell line in which the endogenous Dio3 mRNA is also responsive to those factors [6].

Other interactions of Dio3

  • In addition, we have analyzed the Dio3 gene, located distal to Gtl2 [7].

Analytical, diagnostic and therapeutic context of Dio3

  • Restriction analysis followed by Southern blotting and nucleotide sequencing demonstrated that the Dio3 contains a single exon, 1853 bp in length, that encodes the entire length of the messenger RNA expressed in murine placenta and neonatal skin [5].


  1. Genomic imprinting contributes to thyroid hormone metabolism in the mouse embryo. Tsai, C.E., Lin, S.P., Ito, M., Takagi, N., Takada, S., Ferguson-Smith, A.C. Curr. Biol. (2002) [Pubmed]
  2. The gene locus encoding iodothyronine deiodinase type 3 (Dio3) is imprinted in the fetus and expresses antisense transcripts. Hernandez, A., Fiering, S., Martinez, E., Galton, V.A., St Germain, D. Endocrinology (2002) [Pubmed]
  3. High-resolution map and imprinting analysis of the Gtl2-Dnchc1 domain on mouse chromosome 12. Tierling, S., Dalbert, S., Schoppenhorst, S., Tsai, C.E., Oliger, S., Ferguson-Smith, A.C., Paulsen, M., Walter, J. Genomics (2006) [Pubmed]
  4. Aberrant regulation of imprinted gene expression in Gtl2lacZ mice. Sekita, Y., Wagatsuma, H., Irie, M., Kobayashi, S., Kohda, T., Matsuda, J., Yokoyama, M., Ogura, A., Schuster-Gossler, K., Gossler, A., Ishino, F., Kaneko-Ishino, T. Cytogenet. Genome Res. (2006) [Pubmed]
  5. Isolation and characterization of the mouse gene for the type 3 iodothyronine deiodinase. Hernández, A., Lyon, G.J., Schneider, M.J., St Germain, D.L. Endocrinology (1999) [Pubmed]
  6. Activity and response to serum of the mammalian thyroid hormone deiodinase 3 gene promoter: identification of a conserved enhancer. Hernandez, A., St Germain, D.L. Mol. Cell. Endocrinol. (2003) [Pubmed]
  7. Analysis of candidate imprinted genes linked to Dlk1-Gtl2 using a congenic mouse line. Yevtodiyenko, A., Carr, M.S., Patel, N., Schmidt, J.V. Mamm. Genome (2002) [Pubmed]
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