{"id":"7ba535cd-4301-561d-bdac-574856b3d9ce","stable_key":"fe6af7fc-7372-5c4f-9c2f-2bbf56695397:phosphorus-casr-mouse-null","predicate":"loses_phosphate_response","statement":"The phosphate-induced PTH increase seen in wild-type mouse parathyroid glands was absent in Casr-knockout glands.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"841ba814-1ce3-5ccc-af61-494e7a08a22e","mechanism_event_label":"The mouse glands needed CaSR for this response.","subject":{"id":"233a1669-7faf-55de-9641-e0aaeae89d84","slug":"mouse-casr-null-parathyroid","display_name":"Mouse parathyroid Casr knockout","entity_type_key":"protein_state"},"object":{"id":"9d8536fd-d45c-52b1-a183-533fd1e4f15a","slug":"mouse-pth-secretion","display_name":"Mouse parathyroid hormone secretion","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"841ba814-1ce3-5ccc-af61-494e7a08a22e","stable_key":"fe6af7fc-7372-5c4f-9c2f-2bbf56695397:phosphorus-casr-mouse-null-event","event_type":"biochemical_relationship","label":"The mouse glands needed CaSR for this response.","description":"The phosphate-induced PTH increase seen in wild-type mouse parathyroid glands was absent in Casr-knockout glands.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ee63fe8e-92f3-552f-8049-a5f1fa1e1523","slug":"phosphate-ion","display_name":"Inorganic phosphate (Pi; protonation depends on pH)","entity_type_key":"ion"},"role":"challenge","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"233a1669-7faf-55de-9641-e0aaeae89d84","slug":"mouse-casr-null-parathyroid","display_name":"Mouse parathyroid Casr knockout","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9d8536fd-d45c-52b1-a183-533fd1e4f15a","slug":"mouse-pth-secretion","display_name":"Mouse parathyroid hormone secretion","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/phosphorus-research/31619668.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d\", \"start_char\": 0, \"end_char\": 1144, \"text_sha256\": \"e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Direct phosphate antagonism was tested separately from calcium regulation; concentrations and model are not dietary thresholds.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Phosphorus research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"phosphorus","display_name":"Phosphorus","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The mouse glands needed CaSR for this response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. (2019). https://pubmed.ncbi.nlm.nih.gov/31619668/ DOI: 10.1038/s41467-019-12399-9","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"CaSR reporter cells and freshly isolated parathyroid cells/glands","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":"ad7513ac-9713-53ee-961b-351cf0b41442","evidence_kind":"source_excerpt","locator":"Lines 477-488","start_line":477,"end_line":488,"excerpt":"### phosphorus-casr-mouse-null\nThe phosphate-induced PTH increase seen in wild-type mouse parathyroid glands was absent in Casr-knockout glands.\nCondition category: machinery_impairment\nnutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The mouse glands needed CaSR for this response.\norganism: Mouse\ntissue_or_cell_type: CaSR reporter cells and freshly isolated parathyroid cells/glands\nexperimental_model: CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments\nlimitations: Direct phosphate antagonism was tested separately from calcium regulation; concentrations and model are not dietary thresholds.\nexposure: Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion\nevidence_span: {\"source_cache\": \"artifacts/phosphorus-research/31619668.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d\", \"start_char\": 0, \"end_char\": 1144, \"text_sha256\": \"e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d\"}\n[phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. 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