{"id":"17be85e5-fcc2-5f04-a03e-fd93e57d5451","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-zip4-other-metals","predicate":"loss_led_to","statement":"After enterocyte Zip4 deletion in mice, liver iron, manganese and copper gradually accumulated as the zinc-depletion disease progressed.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"6e3e56a6-097e-5709-8745-4b3ecba2d027","mechanism_event_label":"Loss of zinc uptake disrupted the distribution of several other metals.","subject":{"id":"b704eea7-d5f4-577d-8801-1dd4e946623c","slug":"mouse-enterocyte-slc39a4-knockout","display_name":"Mouse enterocyte-specific Slc39a4 knockout genotype","entity_type_key":"gene"},"object":{"id":"5fc91885-8279-5fc5-ae6f-ef9de343406a","slug":"hepatic-iron-manganese-copper-accumulation","display_name":"Hepatic iron, manganese and copper accumulation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"6e3e56a6-097e-5709-8745-4b3ecba2d027","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-zip4-other-metals-event","event_type":"biochemical_relationship","label":"Loss of zinc uptake disrupted the distribution of several other metals.","description":"After enterocyte Zip4 deletion in mice, liver iron, manganese and copper gradually accumulated as the zinc-depletion disease progressed.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"89bcaf42-b4ab-5760-8c2e-44eace10cee0","slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"},"role":"accumulated_element","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f0459455-8231-513b-8214-7ea5b3259b4b","slug":"manganese","display_name":"Manganese","entity_type_key":"nutrient_element"},"role":"accumulated_element","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9f0afdde-1ec1-5c8a-bb5e-f3b2b75f67f6","slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"},"role":"accumulated_element","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b2399154-5b80-5772-bf7c-d9d80aefb691","slug":"mouse-slc39a4","display_name":"Mouse ZIP4 (Slc39a4)","entity_type_key":"protein"},"role":"affected_transporter","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"b704eea7-d5f4-577d-8801-1dd4e946623c","slug":"mouse-enterocyte-slc39a4-knockout","display_name":"Mouse enterocyte-specific Slc39a4 knockout genotype","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"5fc91885-8279-5fc5-ae6f-ef9de343406a","slug":"hepatic-iron-manganese-copper-accumulation","display_name":"Hepatic iron, manganese and copper accumulation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/zinc-transport-sources/22737083-abstract.txt\", \"locator\": \"Primary indexed abstract; tissue elemental analysis\", \"file_sha256\": \"4643d3986c556a001c45365febbb07095bcdc8bc604e30488d3fb98a23511a4b\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Conditional gene deletion compared with intact controls.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A genetic transport defect is not interchangeable with low intake. Total tissue zinc does not resolve labile versus protein-bound zinc. Tissue accumulation is not proof of systemic nutritional adequacy of the other metals.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zinc research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Loss of zinc uptake disrupted the distribution of several other metals.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zinc-trans-22737083] A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity. (2012). https://pubmed.ncbi.nlm.nih.gov/22737083/ DOI: 10.1371/journal.pgen.1002766","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Small intestine, liver, pancreas","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"70054ab6-8013-5aae-802e-604bab87254b","evidence_kind":"source_excerpt","locator":"Lines 585-597","start_line":585,"end_line":597,"excerpt":"### zinc-trans-zip4-other-metals\nAfter enterocyte Zip4 deletion in mice, liver iron, manganese and copper gradually accumulated as the zinc-depletion disease progressed.\nCondition category: machinery_impairment\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Loss of zinc uptake disrupted the distribution of several other metals.\norganism: Mus musculus\ntissue_or_cell_type: Small intestine, liver, pancreas\nexperimental_model: Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis\nlimitations: A genetic transport defect is not interchangeable with low intake. Total tissue zinc does not resolve labile versus protein-bound zinc. Tissue accumulation is not proof of systemic nutritional adequacy of the other metals.\nexposure: Conditional gene deletion compared with intact controls.\ncross_nutrient: false\nevidence_span: {\"source_cache\": \"artifacts/zinc-transport-sources/22737083-abstract.txt\", \"locator\": \"Primary indexed abstract; tissue elemental analysis\", \"file_sha256\": \"4643d3986c556a001c45365febbb07095bcdc8bc604e30488d3fb98a23511a4b\"}\n[zinc-trans-22737083] A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity. (2012). https://pubmed.ncbi.nlm.nih.gov/22737083/ DOI: 10.1371/journal.pgen.1002766","model_system":"Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zinc-trans-22737083] A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity. (2012). https://pubmed.ncbi.nlm.nih.gov/22737083/ DOI: 10.1371/journal.pgen.1002766","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c5ee0fee-ce5c-58de-905a-10fb0ea0723c","stable_key":"import-6d38d43e-01e4-5641-93be-65654271e242","title":"Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"2e731dd54477ec1254e97df3323e1208d38f1375effed19252e71ab4f600d13a","revision_id":"c72258b9-ac09-5408-9d44-a921ad1f96a3","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}