title: Life without the iodothyronine deiodinases.
abstract: The three iodothyronine deiodinases (D1, D2, and D3) play major roles in determining the tissue and cellular content of the active thyroid hormone, T3. The D1 and D2 5'-deiodinate T4 to T3 and the D3 5-deiodinates T4 and T3 to inactive forms. 5'-Deiodinase-deficient mice (D1/D2KO) have a mild gross phenotype, whereas D3-deficient mice (D3KO) exhibit significant phenotypic abnormalities of the hypothalamic/pituitary/thyroid axis and other organ systems and are not viable in some background strains. The goal of this study was to perform an initial assessment of the phenotype of mice devoid of all deiodinases (D1/D2/D3KO) and determine whether the marked phenotypic abnormalities of the D3KO mouse are exacerbated or mitigated by the absence of the D1 and D2. Relative to D3KO mutants, survival, growth, and fertility were improved in the D1/D2/D3KO mice, although considerably impaired relative to wild-type and D1/D2KO animals. The triple deiodinase-deficient mice also demonstrated normal brain T3 content at postnatal day 6, normal cerebellar expression of the T3-responsive gene hairless at postnatal day 21, and near normalization of their serum thyroid hormone levels as adults, parameters that are abnormal in either the D3KO or the D1/D2KO mutants. These studies demonstrate that within the supportive environment of a research vivarium, mice lacking all three deiodinases can be bred and survive and that at least some of the phenotypic abnormalities resulting from a deficiency of either the D3 5-deiodinase, or the D1 and D2 5'-deiodinase, are mitigated by the simultaneous lack of all three enzymes.
authors.affiliation: The Departments of Physiology and Neurobiology (V.A.G., D.L.S.) and Medicine (D.L.S.), Geisel School of Medicine, Dartmouth University, Lebanon, New Hampshire 03756; Maine Medical Center Research Institute (A.H., D.L.S.), Scarborough, Maine 04074; and Department of Veterans Affairs Medical Center (A.H.), Long Beach, California 90822; Harbor-UCLA Medical Center (A.F.P.), Torrance, California 90509; and Department of Endocrinology (E.d.W.), University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
authors.forename: Valerie Anne
authors.initials: VA
authors.lastname: Galton
authors.forename: Ellis
authors.initials: E
authors.lastname: de Waard
authors.forename: Albert F
authors.initials: AF
authors.lastname: Parlow
authors.forename: Donald L
authors.initials: DL
authors.lastname: St Germain
authors.forename: Arturo
authors.initials: A
authors.lastname: Hernandez
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005298:Fertility / Q000235:genetics; D048788:Growth and Development / Q000235:genetics*; D007453:Iodide Peroxidase / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013963:Thyroid Hormones / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D013963:Thyroid Hormones; D013972:Thyrotropin; D000097564:Iodothyronine Deiodinase Type II; C109812:iodothyronine deiodinase type I; C117274:iodothyronine deiodinase type III