Component

Mouse type 2 iodothyronine deiodinase

Mouse type 2 iodothyronine deiodinase

5 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. D2 activity in P21 forebrain and cerebellum rose almost tenfold in Mct8/Oatp1c1 double-knockout mice despite persistent severe brain hormone depletion.

    Mouse Mct8/Oatp1c1 double knockout → Mouse type 2 iodothyronine deiodinase source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    Selenium-containing D2 processes iodine-containing T4; genetic transport failure persists despite increased enzyme activity.
    evidence_locator
    Figure 4A and Results: Analysis of TH content and metabolism in the brain
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 4A and Results: Analysis of TH content and metabolism in the brain", "start_char": 26902, "end_char": 28402}]
    experimental_model
    Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays
    exposure
    P21 double knockout versus wild type; D2 activity assay.
    limitations
    This is compensatory enzyme activity, not demonstration that selenium supplementation repairs transporter loss.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Mus musculus
    plain_language
    The brain increases local hormone activation machinery, but this cannot replace missing substrate delivery.
    primary_references
    [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
    tissue_or_cell_type
    Forebrain and cerebellum homogenates
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1010–1023

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays · source_derived_draft · unverified_draft

    ### i-met-double-ko-dio2-response D2 activity in P21 forebrain and cerebellum rose almost tenfold in Mct8/Oatp1c1 double-knockout mice despite persistent severe brain hormone depletion. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The brain increases local hormone activation machinery, but this cannot replace missing substrate delivery. organism: Mus musculus tissue_or_cell_type: Forebrain and cerebellum homogenates experimental_model: Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays limitations: This is compensatory enzyme activity, not demonstration that selenium supplementation repairs transporter loss. exposure: P21 double knockout versus wild type; D2 activity assay. cross_nutrient: Selenium-containing D2 processes iodine-containing T4; genetic transport failure persists despite increased enzyme activity. evidence_locator: Figure 4A and Results: Analysis of TH content and metabolism in the brain evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 4A and Results: Analysis of TH content and metabolism in the brain", "start_char": 26902, "end_char": 28402}] [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Adult Dio2-null mice had serum total T3 comparable to wild type despite complete loss of measured D2 activity and elevated serum T4 and TSH.

    Mouse Dio2 knockout → Serum total triiodothyronine concentration source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_locator
    Results: serum hormone levels, Figure 7; Methods page 2146: Assays for Serum T4, T3 and TSH.
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Primary article Results, Figures 7 and 9; Methods: Assays for Serum T4, T3 and TSH, page 2146", "start_char": 17896, "end_char": 18546}, {"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Methods page 2146, total-T3 assay identity and mouse-serum correction", "start_char": 29655, "end_char": 31355}]
    experimental_model
    Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism
    exposure
    Adult mice aged 10–12 weeks; total-T3 Coat-A-Count radioimmunoassay with correction for a nonspecific mouse-serum effect.
    limitations
    Specific mouse compensation; not a diagnostic rule for hidden tissue hypothyroidism in humans.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Mus musculus
    plain_language
    A normal circulating T3 result did not mean that the deleted enzyme was functioning.
    primary_references
    [i-met-11731615] Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. (2001). https://pubmed.ncbi.nlm.nih.gov/11731615/ DOI: 10.1210/mend.15.12.0740
    tissue_or_cell_type
    Serum and surveyed tissues
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1040–1052

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism · source_derived_draft · unverified_draft

    ### i-met-dio2-ko-serum-t3 Adult Dio2-null mice had serum total T3 comparable to wild type despite complete loss of measured D2 activity and elevated serum T4 and TSH. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal circulating T3 result did not mean that the deleted enzyme was functioning. organism: Mus musculus tissue_or_cell_type: Serum and surveyed tissues experimental_model: Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism limitations: Specific mouse compensation; not a diagnostic rule for hidden tissue hypothyroidism in humans. exposure: Adult mice aged 10–12 weeks; total-T3 Coat-A-Count radioimmunoassay with correction for a nonspecific mouse-serum effect. evidence_locator: Results: serum hormone levels, Figure 7; Methods page 2146: Assays for Serum T4, T3 and TSH. evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Primary article Results, Figures 7 and 9; Methods: Assays for Serum T4, T3 and TSH, page 2146", "start_char": 17896, "end_char": 18546}, {"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Methods page 2146, total-T3 assay identity and mouse-serum correction", "start_char": 29655, "end_char": 31355}] [i-met-11731615] Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. (2001). https://pubmed.ncbi.nlm.nih.gov/11731615/ DOI: 10.1210/mend.15.12.0740
    Complete structured claim and evidence

  2. T4 suppressed serum TSH in hypothyroid wild-type mice but not Dio2-null mice; administered T3 suppressed TSH in both genotypes.

    Mouse Dio2 knockout → Serum TSH concentration source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    Selenoenzyme D2 activates an iodine-containing hormone for feedback; knockout is a machinery experiment.
    evidence_locator
    Results: TSH Suppression Studies and Figure 9; pages 2140–2141.
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Primary article Results, Figures 7 and 9; Methods: Assays for Serum T4, T3 and TSH, page 2146", "start_char": 20490, "end_char": 22790}]
    experimental_model
    Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism
    exposure
    Male mice made hypothyroid for four weeks with methimazole/perchlorate; PTU inhibited D1. Subcutaneous T4 3 micrograms/100 g body weight or T3 1.2 micrograms/100 g; serum collected five hours later.
    limitations
    Pharmacologic hormone challenge after thyroid synthesis blockade and D1 inhibition; not a human dosing rule or dietary selenium-deficiency experiment.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Mus musculus
    plain_language
    T3 bypassed the missing local T4-activation step in this feedback experiment.
    primary_references
    [i-met-11731615] Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. (2001). https://pubmed.ncbi.nlm.nih.gov/11731615/ DOI: 10.1210/mend.15.12.0740
    tissue_or_cell_type
    Pituitary feedback and serum TSH
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1025–1038

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism · source_derived_draft · unverified_draft

    ### i-met-dio2-t4-feedback T4 suppressed serum TSH in hypothyroid wild-type mice but not Dio2-null mice; administered T3 suppressed TSH in both genotypes. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: T3 bypassed the missing local T4-activation step in this feedback experiment. organism: Mus musculus tissue_or_cell_type: Pituitary feedback and serum TSH experimental_model: Dio2-null mice and wild-type littermates, including hormone challenge after hypothyroidism limitations: Pharmacologic hormone challenge after thyroid synthesis blockade and D1 inhibition; not a human dosing rule or dietary selenium-deficiency experiment. exposure: Male mice made hypothyroid for four weeks with methimazole/perchlorate; PTU inhibited D1. Subcutaneous T4 3 micrograms/100 g body weight or T3 1.2 micrograms/100 g; serum collected five hours later. cross_nutrient: Selenoenzyme D2 activates an iodine-containing hormone for feedback; knockout is a machinery experiment. evidence_locator: Results: TSH Suppression Studies and Figure 9; pages 2140–2141. evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/11731615.txt", "locator": "Primary article Results, Figures 7 and 9; Methods: Assays for Serum T4, T3 and TSH, page 2146", "start_char": 20490, "end_char": 22790}] [i-met-11731615] Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. (2001). https://pubmed.ncbi.nlm.nih.gov/11731615/ DOI: 10.1210/mend.15.12.0740
    Complete structured claim and evidence

  3. At postnatal day 21, double-knockout forebrain T3 content was approximately 10% of wild type, whereas Oatp1c1 single-knockout forebrain T3 was preserved.

    Mouse Mct8/Oatp1c1 double knockout → Brain triiodothyronine content source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_locator
    Figure 3B and Results: Analysis of TH content and metabolism in the brain
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3B and Results: Analysis of TH content and metabolism in the brain", "start_char": 26251, "end_char": 27951}]
    experimental_model
    Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays
    exposure
    P21, n=8 per genotype; hormone content measurements.
    limitations
    The content result is local to mouse forebrain and this developmental time.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Mus musculus
    plain_language
    Losing both transport routes overwhelms the compensation seen after one loss.
    primary_references
    [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
    tissue_or_cell_type
    Perfused forebrain
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 996–1008

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays · source_derived_draft · unverified_draft

    ### i-met-double-ko-brain-t3 At postnatal day 21, double-knockout forebrain T3 content was approximately 10% of wild type, whereas Oatp1c1 single-knockout forebrain T3 was preserved. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Losing both transport routes overwhelms the compensation seen after one loss. organism: Mus musculus tissue_or_cell_type: Perfused forebrain experimental_model: Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays limitations: The content result is local to mouse forebrain and this developmental time. exposure: P21, n=8 per genotype; hormone content measurements. evidence_locator: Figure 3B and Results: Analysis of TH content and metabolism in the brain evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3B and Results: Analysis of TH content and metabolism in the brain", "start_char": 26251, "end_char": 27951}] [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
    Complete structured claim and evidence

  4. Brain uptake of injected radiolabeled T4 was strongly reduced in Mct8/Oatp1c1 double-knockout mice; either single knockout retained roughly half the wild-type uptake.

    Mouse Mct8/Oatp1c1 double knockout → Thyroxine entry into brain source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_locator
    Figure 3A and Results: In vivo T4 transport studies
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3A and Results: In vivo T4 transport studies", "start_char": 23660, "end_char": 25360}]
    experimental_model
    Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays
    exposure
    Adults received 1.2 microcuries 125I-T4 intraperitoneally; n=3 per genotype and time point.
    limitations
    Tracer accumulation is a transport measurement; murine redundancy is not proof of equivalent human compensation.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Mus musculus
    plain_language
    The two mouse transporters provide partly overlapping routes into the brain.
    primary_references
    [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
    tissue_or_cell_type
    Brain after systemic tracer injection
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 982–994

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays · source_derived_draft · unverified_draft

    ### i-met-double-ko-t4-entry Brain uptake of injected radiolabeled T4 was strongly reduced in Mct8/Oatp1c1 double-knockout mice; either single knockout retained roughly half the wild-type uptake. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two mouse transporters provide partly overlapping routes into the brain. organism: Mus musculus tissue_or_cell_type: Brain after systemic tracer injection experimental_model: Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays limitations: Tracer accumulation is a transport measurement; murine redundancy is not proof of equivalent human compensation. exposure: Adults received 1.2 microcuries 125I-T4 intraperitoneally; n=3 per genotype and time point. evidence_locator: Figure 3A and Results: In vivo T4 transport studies evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3A and Results: In vivo T4 transport studies", "start_char": 23660, "end_char": 25360}] [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324
    Complete structured claim and evidence

In the sources

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