{"id":"1bdf95b0-2f00-5923-a043-75a8873e9f03","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:vdr-loss-hypocalcemia","predicate":"loss_of_function_reduces","statement":"VDR-ablated mice develop hypocalcemia around postnatal day 21 with rising PTH.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"4dee512f-b5ec-596f-afca-a3ca28e9865d","mechanism_event_label":"Vitamin D receptor failure disrupts calcium regulation.","subject":{"id":"d725020b-bacc-5e90-b370-cda246025c91","slug":"vdr","display_name":"Vitamin D receptor / VDR","entity_type_key":"protein"},"object":{"id":"068b1eb6-c8bf-59d3-98a0-df623ad01b52","slug":"serum-calcium-concentration","display_name":"Serum calcium concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4dee512f-b5ec-596f-afca-a3ca28e9865d","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:vdr-loss-hypocalcemia-event","event_type":"biochemical_relationship","label":"Vitamin D receptor failure disrupts calcium regulation.","description":"VDR-ablated mice develop hypocalcemia around postnatal day 21 with rising PTH.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d725020b-bacc-5e90-b370-cda246025c91","slug":"vdr","display_name":"Vitamin D receptor / VDR","entity_type_key":"protein"},"role":"impaired_machinery","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"regulated_ion","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e162b0ab-1449-5471-b3c3-4638a0fa3a96","slug":"pth","display_name":"Parathyroid hormone / PTH","entity_type_key":"protein"},"role":"compensatory_hormone","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"068b1eb6-c8bf-59d3-98a0-df623ad01b52","slug":"serum-calcium-concentration","display_name":"Serum calcium concentration","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":"experimental_model","value_text":"Mice with targeted disruption of the VDR DNA-binding domain","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Global receptor deletion; not isolated dietary calcium shortage.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Calcium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"calcium","display_name":"Calcium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Vitamin D receptor failure disrupts calcium regulation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[li1997] Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC23277/ DOI: 10.1073/pnas.94.18.9831","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Systemic mineral metabolism","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":"d2e376f1-3761-5155-8866-480c49e7fc65","evidence_kind":"source_excerpt","locator":"Lines 135-144","start_line":135,"end_line":144,"excerpt":"### vdr-loss-hypocalcemia\nVDR-ablated mice develop hypocalcemia around postnatal day 21 with rising PTH.\nCondition category: machinery_impairment\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Vitamin D receptor failure disrupts calcium regulation.\norganism: Mus musculus\ntissue_or_cell_type: Systemic mineral metabolism\nexperimental_model: Mice with targeted disruption of the VDR DNA-binding domain\nlimitations: Global receptor deletion; not isolated dietary calcium shortage.\n[li1997] Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC23277/ DOI: 10.1073/pnas.94.18.9831","model_system":"Mice with targeted disruption of the VDR DNA-binding domain","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [li1997] Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC23277/ DOI: 10.1073/pnas.94.18.9831","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3c083fa0-59c6-50e9-af42-678d0e3c1006","stable_key":"import-434e1e27-eb90-583a-956b-62472726ffba","title":"Calcium: mechanism-first literature curation (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":"965c934d6b147f2b62f8d45ce6d7a87681a600bfe5c46a585b4704889afd3fc1","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[{"id":"80542f5e-be46-5ff4-875e-905ba7057f67","title":"Mineral delivery can bypass part of VDR loss","kind":"context_difference","status":"qualified","why":"VDR deletion causes hypocalcemia under ordinary experimental feeding, but a combined rescue diet normalizes ionized calcium.","resolution":"Curation interpretation: Receptor loss and low intake are separate triggers; do not attribute combined-diet rescue solely to calcium.","created_at":"2026-09-17 08:08:54","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/80542f5e-be46-5ff4-875e-905ba7057f67","sides":[{"conflict_id":"80542f5e-be46-5ff4-875e-905ba7057f67","ordinal":0,"label":"Vitamin D receptor failure disrupts calcium regulation.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":135,"end_line":144,"quote":"### vdr-loss-hypocalcemia\nVDR-ablated mice develop hypocalcemia around postnatal day 21 with rising PTH.\nCondition category: machinery_impairment\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Vitamin D receptor failure disrupts calcium regulation.\norganism: Mus musculus\ntissue_or_cell_type: Systemic mineral metabolism\nexperimental_model: Mice with targeted disruption of the VDR DNA-binding domain\nlimitations: Global receptor deletion; not isolated dietary calcium shortage.\n[li1997] Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC23277/ DOI: 10.1073/pnas.94.18.9831","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["1bdf95b0-2f00-5923-a043-75a8873e9f03"]},{"conflict_id":"80542f5e-be46-5ff4-875e-905ba7057f67","ordinal":1,"label":"Dietary mineral delivery can bypass part of receptor failure.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":146,"end_line":156,"quote":"### vdr-null-mineral-diet-rescue\nA mineral/lactose rescue diet normalizes ionized calcium in VDR-ablated mice.\nCondition category: machinery_impairment\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Dietary mineral delivery can bypass part of receptor failure.\norganism: Mus musculus\ntissue_or_cell_type: Intestine and blood\nexperimental_model: VDR-ablated mice and controls fed a mineral/lactose rescue diet\nlimitations: Combined dietary intervention; cannot attribute rescue to calcium alone.\nreported_effect: normalizing\n[li1998] Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice (1998). https://pubmed.ncbi.nlm.nih.gov/9751523/ DOI: 10.1210/endo.139.10.6262","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["54be0e0e-5d72-5bbb-837e-fc2443ff902b"]}]}],"research":null}