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The mouse Dio3 gene codes for the type 3 iodothyronine deiodinase (D3), a conserved selenocysteine-containing enzyme that inactivates thyroid hormones and is highly expressed during early development. The mouse Dio3 gene and its human homolog map to chromosomal regions that are known to contain imprinted genes. We assessed the allelic expression of the Dio3 using a mouse model in which the gene had been inactivated by the introduction of a critical mutation in the selenocysteine codon. We compared Dio3 gene expression in fetuses that were either wild type or heterozygous (+/−Dio3) for the mutation. D3 enzymatic activities in the head, limbs, liver and body of heterozygous fetuses (E14 to E18) that inherited the mutation from the mother were no different from those found in their wild type littermates. However, D3 activities in heterozygous animals that inherited the mutation from the father were …