{"id":"17195e28-e7b2-526d-9f75-e44ae5426811","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-gulo-depletion-epo-preserved","predicate":"depletion-does-not-abolish-hypoxic-induction","statement":"Male Gulo-null mice deprived of vitamin C for approximately five weeks retained a robust plasma erythropoietin response to 24 h at 8% oxygen, similar to supplemented controls, despite plasma ascorbate at or below 1 µM and scorbutic weight loss.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"61a9e9fb-60f2-5470-951a-3138640d3736","mechanism_event_label":"Even severely vitamin-C-depleted mice retained this measured hormonal response to low oxygen.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"5edaae24-82b7-570f-9510-0aba98ebde06","slug":"circulating-erythropoietin","display_name":"Circulating erythropoietin concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"61a9e9fb-60f2-5470-951a-3138640d3736","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-gulo-depletion-epo-preserved-event","event_type":"biochemical_relationship","label":"Even severely vitamin-C-depleted mice retained this measured hormonal response to low oxygen.","description":"Male Gulo-null mice deprived of vitamin C for approximately five weeks retained a robust plasma erythropoietin response to 24 h at 8% oxygen, similar to supplemented controls, despite plasma ascorbate at or below 1 µM and scorbutic weight loss.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"da1a7137-08f2-5a36-8bb6-377fbd32e327","slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"},"role":"nutrient context","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"899c7ab0-6f81-5b38-a6bd-fbb33d66ac8d","slug":"oxygen","display_name":"Molecular oxygen","entity_type_key":"small_molecule"},"role":"hypoxic stimulus","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5edaae24-82b7-570f-9510-0aba98ebde06","slug":"circulating-erythropoietin","display_name":"Circulating erythropoietin concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","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_location","value_text":"Figure 5C–D; Animal studies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Dietary withdrawal in adult male Gulo-null mice with supplemented-genotype controls","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Maintenance 0.33 g/L ascorbic acid drinking water; withdrawal about 35–36 days; 8% inspired oxygen for 24 h.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Dietary deficiency in a synthesis-null animal; does not establish that every HIF target or tissue is unaffected, nor a safe human deficiency threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin C research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Even severely vitamin-C-depleted mice retained this measured hormonal response to low oxygen.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[c-reg-nytko] Vitamin C is dispensable for oxygen sensing in vivo. (2011). https://pubmed.ncbi.nlm.nih.gov/21346252/ DOI: 10.1182/blood-2010-09-307637","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Plasma erythropoietin; kidney Epo mRNA supporting endpoint","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"89e63e72-e2e2-50a6-b981-41e8595742c4","evidence_kind":"source_excerpt","locator":"Lines 1187-1199","start_line":1187,"end_line":1199,"excerpt":"### c-reg-gulo-depletion-epo-preserved\nMale Gulo-null mice deprived of vitamin C for approximately five weeks retained a robust plasma erythropoietin response to 24 h at 8% oxygen, similar to supplemented controls, despite plasma ascorbate at or below 1 µM and scorbutic weight loss.\nCondition category: nutrient_deficiency\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Even severely vitamin-C-depleted mice retained this measured hormonal response to low oxygen.\norganism: Mus musculus\ntissue_or_cell_type: Plasma erythropoietin; kidney Epo mRNA supporting endpoint\nexperimental_model: Dietary withdrawal in adult male Gulo-null mice with supplemented-genotype controls\nlimitations: Dietary deficiency in a synthesis-null animal; does not establish that every HIF target or tissue is unaffected, nor a safe human deficiency threshold.\nexposure: Maintenance 0.33 g/L ascorbic acid drinking water; withdrawal about 35–36 days; 8% inspired oxygen for 24 h.\ncross_nutrient: false\nevidence_location: Figure 5C–D; Animal studies\n[c-reg-nytko] Vitamin C is dispensable for oxygen sensing in vivo. (2011). https://pubmed.ncbi.nlm.nih.gov/21346252/ DOI: 10.1182/blood-2010-09-307637","model_system":"Dietary withdrawal in adult male Gulo-null mice with supplemented-genotype controls","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [c-reg-nytko] Vitamin C is dispensable for oxygen sensing in vivo. (2011). https://pubmed.ncbi.nlm.nih.gov/21346252/ DOI: 10.1182/blood-2010-09-307637","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"fa811221-13bd-5c10-adc1-eaf097c7703c","stable_key":"import-cb568d28-484a-5c2e-9fcc-2d780358e514","title":"Vitamin C: mechanisms, 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":"b7fd83f956abb81855f2ea23199ba14e465cd91f4a2ac560277ec21ddafd7bfc","revision_id":"6cde9bbb-d712-5746-82a6-85b144253efa","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}