{"id":"6326dc27-bbc2-533e-909f-a13c759bfec4","stable_key":"18100170-a014-51c3-adeb-9dab4162b8cc:mt-stress-activity","predicate":"decreases_in_recorded_experiment","statement":"Stressed metallothionein-overexpressing mice had reduced active thymulin despite normal-range plasma zinc and preserved zinc-recoverable thymulin activity.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"d355b92d-5b7e-5fe7-969e-4ab3c18ae0c5","mechanism_event_label":"Stressed metallothionein-overexpressing mice had reduced active thymulin despite normal-range plasma zinc and preserved zinc-recoverable thymulin activity.","subject":{"id":"8c7ac859-5fa9-5ace-bf14-e18cf53dd402","slug":"mouse-metallothionein-overexpression","display_name":"Experimental mouse metallothionein overexpression","entity_type_key":"cellular_process"},"object":{"id":"8cf03312-bba2-5625-b1ad-abc85d7bddc5","slug":"mouse-thymulin-bioactivity","display_name":"Mouse thymulin bioassay activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d355b92d-5b7e-5fe7-969e-4ab3c18ae0c5","stable_key":"18100170-a014-51c3-adeb-9dab4162b8cc:mt-stress-activity-event","event_type":"experimental_observation","label":"Stressed metallothionein-overexpressing mice had reduced active thymulin despite normal-range plasma zinc and preserved zinc-recoverable thymulin activity.","description":"Metallothionein is not simply beneficial or harmful. A 2002 mouse study found that stressed metallothionein-overexpressing animals had reduced active thymulin and NK-cell activity despite normal-range plasma zinc and preserved zinc-recoverable thymulin activity. Higher corticosterone, liver zinc–metallothionein and reduced thymic cortex accompanied the phenotype. This supports investigating **zinc distribution and stress**, but does not prove that metallothionein directly starved the peptide in TECs or mediated every immune change. Liver storage, TEC delivery and serum bioactivity are different compartments and measurements. [Mouse stress and zinc-distribution study](https://pmc.ncbi.nlm.nih.gov/articles/PMC7127331/)","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8c7ac859-5fa9-5ace-bf14-e18cf53dd402","slug":"mouse-metallothionein-overexpression","display_name":"Experimental mouse metallothionein overexpression","entity_type_key":"cellular_process"},"role":"tested factor","stoichiometry":null,"state_label":"Metallothionein overexpression under stress","sequence_order":0,"notes":""},{"entity":{"id":"8cf03312-bba2-5625-b1ad-abc85d7bddc5","slug":"mouse-thymulin-bioactivity","display_name":"Mouse thymulin bioassay activity","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""},{"entity":{"id":"23819462-9bdf-5856-beac-68b3dca9cf85","slug":"thymulin","display_name":"Thymulin","entity_type_key":"peptide"},"role":"bioassayed peptide","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"compartment-dependent metal","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"395ad189-2675-5ae7-89fa-40f9925383bb","slug":"mouse-thymulin-zinc-recoverable-activity","display_name":"Mouse zinc-recoverable thymulin activity","entity_type_key":"cellular_process"},"role":"preserved recovery readout","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Full text obtained; relevant results/methods inspected. This does not assert exhaustive figure/data reanalysis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"overexpression","comparator":"Study control mice","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"mouse-metallothionein-overexpression","display_name":"Experimental mouse metallothionein overexpression","entity_type_key":"cellular_process"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"Metallothionein overexpression under stress\", \"comparator\": \"Study control mice\", \"endpoint\": \"Stressed metallothionein-overexpressing mice had reduced active thymulin despite normal-range plasma zinc and preserved zinc-recoverable thymulin activity.\", \"effect_direction\": \"decrease\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"mouse-metallothionein-overexpression\", \"state\": \"overexpression\"}, {\"entity_slug\": null, \"state\": \"experimental stress\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Stressed metallothionein-overexpressing mice; liver zinc storage, plasma zinc and thymic changes were distinct measurements.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Stressed metallothionein-overexpressing mice had reduced active thymulin despite normal-range plasma zinc and preserved zinc-recoverable thymulin activity.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Metallothioneins (I+II) and thyroid–thymus axis efficiency in old mice: role of corticosterone and zinc supply | 2002 | DOI 10.1016/S0047-6374(01)00414-6 | PMID 11850030 | https://pmc.ncbi.nlm.nih.gov/articles/PMC7127331/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 48-48; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"17648d64-53fa-5e39-a158-a65b0217f5f7","evidence_kind":"source_excerpt","locator":"Lines 48-48","start_line":48,"end_line":48,"excerpt":"Metallothionein is not simply beneficial or harmful. A 2002 mouse study found that stressed metallothionein-overexpressing animals had reduced active thymulin and NK-cell activity despite normal-range plasma zinc and preserved zinc-recoverable thymulin activity. Higher corticosterone, liver zinc–metallothionein and reduced thymic cortex accompanied the phenotype. This supports investigating **zinc distribution and stress**, but does not prove that metallothionein directly starved the peptide in TECs or mediated every immune change. Liver storage, TEC delivery and serum bioactivity are different compartments and measurements. [Mouse stress and zinc-distribution study](https://pmc.ncbi.nlm.nih.gov/articles/PMC7127331/)","model_system":"Stressed metallothionein-overexpressing mice; liver zinc storage, plasma zinc and thymic changes were distinct measurements.","directness":"reported_statement","verification_status":"source_recorded","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. Not a verbatim quotation from a primary paper.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"e1871d49-9c6b-547b-a1bb-6e2b9270ca89","stable_key":"import-18100170-a014-51c3-adeb-9dab4162b8cc","title":"Thymulin: detailed mechanisms of action (reviewed 3 October 2026)","document_type":"imported_text","citation_label":"Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. 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