{"id":"58cfed93-8dc1-5492-a586-eca0a8f7843b","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zn-sig-zip7-er-stress","predicate":"increased","statement":"Intestinal epithelial Zip7 deletion increased ER-stress responses in proliferative progenitor cells and was followed by substantial progenitor-cell death.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"7e9e5677-4e95-5bd7-8c45-38a4f764f3c0","mechanism_event_label":"Loss of zinc distribution machinery stressed the cells that renew the intestinal lining.","subject":{"id":"5d313543-cdb5-51cc-bf9a-0b0385ea84ee","slug":"mouse-intestinal-zip7-loss","display_name":"Mouse intestinal epithelial ZIP7 loss","entity_type_key":"cellular_process"},"object":{"id":"b552beea-0f46-568a-a393-8c398e1b8c00","slug":"intestinal-crypt-er-stress","display_name":"Intestinal crypt endoplasmic-reticulum stress","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7e9e5677-4e95-5bd7-8c45-38a4f764f3c0","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zn-sig-zip7-er-stress-event","event_type":"biochemical_relationship","label":"Loss of zinc distribution machinery stressed the cells that renew the intestinal lining.","description":"Intestinal epithelial Zip7 deletion increased ER-stress responses in proliferative progenitor cells and was followed by substantial progenitor-cell death.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"22580582-85ca-5c49-a512-fc7f90cee70a","slug":"mouse-slc39a7","display_name":"Mouse ZIP7 / Slc39a7","entity_type_key":"protein"},"role":"affected_transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3c941486-6e86-591a-9d5a-b7f2d14d85ce","slug":"intestinal-progenitor-survival","display_name":"Intestinal progenitor-cell survival","entity_type_key":"cellular_process"},"role":"reduced_endpoint","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5d313543-cdb5-51cc-bf9a-0b0385ea84ee","slug":"mouse-intestinal-zip7-loss","display_name":"Mouse intestinal epithelial ZIP7 loss","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b552beea-0f46-568a-a393-8c398e1b8c00","slug":"intestinal-crypt-er-stress","display_name":"Intestinal crypt endoplasmic-reticulum stress","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":"Mouse ZIP7 / Slc39a7 (affected_transporter); Intestinal progenitor-cell survival (reduced_endpoint)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/zinc-signaling-sources/27736879-abstract.txt\", \"locator\": \"Primary indexed abstract\", \"file_sha256\": \"4ce8fe391aff141b5145e4122917ca1c1817273ab0dd55c7a936b687d9dacdd6\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Conditional intestinal Zip7-deficient mice and organoids","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Intestinal epithelial versus Lgr5-cell-specific deletion; zinc supplementation comparison.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell lineage and tissue context matter. Supplementation failing to rescue a transporter defect is not evidence that ordinary dietary zinc replacement fails.","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 distribution machinery stressed the cells that renew the intestinal lining.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Intestinal crypts, progenitor cells and organoids","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":"695e06fb-8d8f-567b-98ea-b1e292dcd769","evidence_kind":"source_excerpt","locator":"Lines 1125-1137","start_line":1125,"end_line":1137,"excerpt":"### zn-sig-zip7-er-stress\nIntestinal epithelial Zip7 deletion increased ER-stress responses in proliferative progenitor cells and was followed by substantial progenitor-cell death.\nCondition category: machinery_impairment\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Loss of zinc distribution machinery stressed the cells that renew the intestinal lining.\norganism: Mus musculus\ntissue_or_cell_type: Intestinal crypts, progenitor cells and organoids\nexperimental_model: Conditional intestinal Zip7-deficient mice and organoids\nlimitations: Cell lineage and tissue context matter. Supplementation failing to rescue a transporter defect is not evidence that ordinary dietary zinc replacement fails.\nexposure: Intestinal epithelial versus Lgr5-cell-specific deletion; zinc supplementation comparison.\ncross_nutrient: Mouse ZIP7 / Slc39a7 (affected_transporter); Intestinal progenitor-cell survival (reduced_endpoint)\nevidence_span: {\"source_cache\": \"artifacts/zinc-signaling-sources/27736879-abstract.txt\", \"locator\": \"Primary indexed abstract\", \"file_sha256\": \"4ce8fe391aff141b5145e4122917ca1c1817273ab0dd55c7a936b687d9dacdd6\"}\n[zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349","model_system":"Conditional intestinal Zip7-deficient mice and organoids","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349","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}