{"id":"3b29dbdf-9fdb-5e75-8f03-22b585ec1309","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-trans-hepatic-zip14-loss-no-systemic-overload","predicate":"does_not_increase","statement":"Liver-specific Zip14 knockout reduced liver manganese without producing manganese accumulation in other tissues under the reported normal conditions.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"2d6d64e0-cd61-5b4d-ace6-5115d900bbb9","mechanism_event_label":"Liver ZIP14 loss alone did not reproduce whole-body manganese overload.","subject":{"id":"3cf1b1e4-b601-55d4-a62b-ff7f51787136","slug":"mouse-hepatocyte-slc39a14-knockout","display_name":"Mouse liver-specific Slc39a14 knockout genotype","entity_type_key":"gene"},"object":{"id":"b619b064-2985-53f4-b3ae-cc44509d5cde","slug":"extrahepatic-manganese-accumulation","display_name":"Extrahepatic manganese accumulation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2d6d64e0-cd61-5b4d-ace6-5115d900bbb9","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-trans-hepatic-zip14-loss-no-systemic-overload-event","event_type":"biochemical_relationship","label":"Liver ZIP14 loss alone did not reproduce whole-body manganese overload.","description":"Liver-specific Zip14 knockout reduced liver manganese without producing manganese accumulation in other tissues under the reported normal conditions.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a8082b11-c484-5792-bb81-48e8e699cbe4","slug":"manganese-ion","display_name":"Mn2+","entity_type_key":"ion"},"role":"transported_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9e0e70ec-aa5b-584d-a6ea-28c400cb3100","slug":"mouse-slc39a14","display_name":"Mouse ZIP14 (Slc39a14)","entity_type_key":"protein"},"role":"affected_transporter","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"3cf1b1e4-b601-55d4-a62b-ff7f51787136","slug":"mouse-hepatocyte-slc39a14-knockout","display_name":"Mouse liver-specific Slc39a14 knockout genotype","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b619b064-2985-53f4-b3ae-cc44509d5cde","slug":"extrahepatic-manganese-accumulation","display_name":"Extrahepatic manganese accumulation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"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":"experimental_model","value_text":"Liver-specific Slc39a14 knockout mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Liver-specific Slc39a14 knockout under normal study conditions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A conditional negative result does not exclude a hepatic contribution when intestinal clearance is also impaired.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Manganese research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"manganese","display_name":"Manganese","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Liver ZIP14 loss alone did not reproduce whole-body manganese overload.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. (2019). https://pubmed.ncbi.nlm.nih.gov/31028174/ DOI: 10.1074/jbc.ra119.008762","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver and extrahepatic tissues","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":"5e1e443e-fe16-5ff4-8e88-6f75a63a5d14","evidence_kind":"source_excerpt","locator":"Lines 214-225","start_line":214,"end_line":225,"excerpt":"### mn-trans-hepatic-zip14-loss-no-systemic-overload\nLiver-specific Zip14 knockout reduced liver manganese without producing manganese accumulation in other tissues under the reported normal conditions.\nCondition category: machinery_impairment\nnutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Liver ZIP14 loss alone did not reproduce whole-body manganese overload.\norganism: Mus musculus\ntissue_or_cell_type: Liver and extrahepatic tissues\nexperimental_model: Liver-specific Slc39a14 knockout mice\nlimitations: A conditional negative result does not exclude a hepatic contribution when intestinal clearance is also impaired.\nexposure: Liver-specific Slc39a14 knockout under normal study conditions.\ncross_nutrient: false\n[mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. 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