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].

References