{"id":"90d2c905-4393-588f-9131-30562a90feac","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-heph-cp-low-blood-iron","predicate":"combined_loss_with_cp_reduces","statement":"Whole-body Heph/Cp double-knockout mice developed severe anemia and low serum iron despite iron-loaded tissues.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ff665525-0041-5c39-b5ea-94adb6ffae2a","mechanism_event_label":"The body had iron, but much of it was in the wrong places.","subject":{"id":"09ce59ec-fb34-5cf4-affe-948b7dd6e8a2","slug":"mouse-heph","display_name":"Mouse hephaestin Heph","entity_type_key":"protein"},"object":{"id":"64533ebe-ded0-52c9-a31a-3c60016f83ed","slug":"mouse-circulating-iron-availability","display_name":"Mouse circulating iron availability","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ff665525-0041-5c39-b5ea-94adb6ffae2a","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-heph-cp-low-blood-iron-event","event_type":"biochemical_relationship","label":"The body had iron, but much of it was in the wrong places.","description":"Whole-body Heph/Cp double-knockout mice developed severe anemia and low serum iron despite iron-loaded tissues.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"34665f8c-8d15-577c-9244-75a3c6ca61f8","slug":"mouse-cp","display_name":"Mouse ceruloplasmin Cp","entity_type_key":"protein"},"role":"second deleted ferroxidase","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"09ce59ec-fb34-5cf4-affe-948b7dd6e8a2","slug":"mouse-heph","display_name":"Mouse hephaestin Heph","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"64533ebe-ded0-52c9-a31a-3c60016f83ed","slug":"mouse-circulating-iron-availability","display_name":"Mouse circulating iron availability","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/copper-research/30182051.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72\", \"start_char\": 0, \"end_char\": 1882, \"text_sha256\": \"57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Whole-body and intestine-specific Heph/Cp double-knockout mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Combined or tissue-specific deletion; oral iron tracer","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Copper research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The body had iron, but much of it was in the wrong places.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Intestine, liver, heart, pancreas and blood","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":"6eaba1ae-5dec-5bec-bbf2-485493e6ed39","evidence_kind":"source_excerpt","locator":"Lines 819-830","start_line":819,"end_line":830,"excerpt":"### copper-heph-cp-low-blood-iron\nWhole-body Heph/Cp double-knockout mice developed severe anemia and low serum iron despite iron-loaded tissues.\nCondition category: machinery_impairment\nnutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The body had iron, but much of it was in the wrong places.\norganism: Mouse\ntissue_or_cell_type: Intestine, liver, heart, pancreas and blood\nexperimental_model: Whole-body and intestine-specific Heph/Cp double-knockout mice\nlimitations: Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route.\nexposure: Combined or tissue-specific deletion; oral iron tracer\nevidence_span: {\"source_cache\": \"artifacts/copper-research/30182051.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72\", \"start_char\": 0, \"end_char\": 1882, \"text_sha256\": \"57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72\"}\n[copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006","model_system":"Whole-body and intestine-specific Heph/Cp double-knockout mice","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"9afba495-cbdc-51aa-998e-70a930dba3be","stable_key":"import-0ad8610d-d575-5870-b7cd-763a9f750783","title":"Copper: transport, cuproenzymes, deficiency, excess 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. 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