Impairment of the selenoenzyme type I iodothyronine deiodinase in C3H/He mice.

Abstract

Type I iodothyronine deiodinase (ID-I) activity is impaired in C3H/He (C3H) mice compared with BALB/c and C57BL/6N (C57) mice. In this study we compared ID-I activity and protein labeling with N-bromoacetyl(-)[125I]T3 (BrAc[125I]T3) or 75Se in liver microsomes of C3H and C57 mice. Hepatic ID-I activity in C3H mice was highly variable with a median of only 18% of that in C57 mice. However, C3H mice had normal serum T4 and T3 levels, although serum reverse T3 was increased. The 28-kilodalton (kDa) ID-I protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of BrAc[125I]T3-labeled microsomes. Labeling of this protein was virtually undetectable in C3H samples with low enzyme activity. ID-I activity in liver microsomes was strongly decreased in Se-deficient mice, which was paralleled by a drastic decrease in BrAc[125I]T3-labeling of the 28-kDa band compared with control mice. Labeling of ID-I with 75Se was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of liver microsomes of [75Se]selenite-injected mice. 75Se labeling of the 28-kDa band was markedly higher in Se-deficient than in control mice and was also markedly higher in C57 than in C3H mice. Finally, liver ID-I messenger RNA (mRNA) was measured on Northern blots using a rat ID-I complementary DNA probe. Messenger RNA levels correlated strongly with ID-I activity, showing a significant decrease in C3H mice. We conclude that in mice, like in rats and humans, ID-I is a selenoprotein. ID-I activity is impaired in C3H mice because of decreased transcription of the ID-I gene or reduced stability of the mRNA.

Hepatocyte Nuclear Factor 4α Contributes to Thyroid Hormone Homeostasis by Cooperatively Regulating the Type 1 Iodothyronine Deiodinase Gene with GATA4 and Krüppel-Like Transcription Factor 9

“…S1 in the supplemental material). Currently, four mouse models have been reported with various deficiencies in the deiodinases: mice with a targeted disruption of the Dio1 gene (Dio1KO) (52); mice with a targeted disruption of the Dio2 gene (Dio2KO mice) (51); C3H mice, which have genetically low levels of Dio1 (7,53); and Dio2KO mice backcrossed into a C3H background (13). Each of these animals has a normal serum T 3 concentration and an increased serum T 4 concentration (8).…”

Physiological and genetic analyses of inbred mouse strains with a type I iodothyronine 5' deiodinase deficiency.

“…(45) reported 5'DI activities, mRNA, and serum hormone levels in C3H and B6 mice, initiating their studies after informal discussions with one of us (A.P.). In contrast to our findings, they observed highly variable hepatic 51DI activities in C3H mice, though the mean was 18% of that in the B6 strain.…”

Deiodinases: implications of the local control of thyroid hormone action

“…tion of the Dio2 gene (D2KO mice) (41); C3H mice, which have genetically low levels of D1 (42,43); and D2KO mice backcrossed into a C3H background (C3H/D2KO mice) (44). Remarkably, each of these animals has a normal serum T3 concentration and an increased serum T4 concentration.…”