{"id":"4c112ea7-5682-5ea7-ace1-8f950242970f","stable_key":"4df6a932-097e-563a-91fe-5dceec471ffd:chloride-clcnk2-diuretics","predicate":"loss_of_function_changes","statement":"ClC-K2-null mice lacked the usual furosemide natriuretic response and had a severely blunted thiazide response.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"5d91ac9e-67c4-5d00-8f97-f747f61b7e26","mechanism_event_label":"A transporter defect changed how two diuretic classes worked.","subject":{"id":"e6d8bc95-67e7-53b8-be59-e4b2e2531104","slug":"mouse-clcnk2","display_name":"Mouse ClC-K2 basolateral chloride channel / Clcnk2","entity_type_key":"protein"},"object":{"id":"c3172b1b-4ea1-5919-a707-80602377fdb4","slug":"diuretic-response","display_name":"Renal response to loop diuretics","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"5d91ac9e-67c4-5d00-8f97-f747f61b7e26","stable_key":"4df6a932-097e-563a-91fe-5dceec471ffd:chloride-clcnk2-diuretics-event","event_type":"biochemical_relationship","label":"A transporter defect changed how two diuretic classes worked.","description":"ClC-K2-null mice lacked the usual furosemide natriuretic response and had a severely blunted thiazide response.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e6d8bc95-67e7-53b8-be59-e4b2e2531104","slug":"mouse-clcnk2","display_name":"Mouse ClC-K2 basolateral chloride channel / Clcnk2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c3172b1b-4ea1-5919-a707-80602377fdb4","slug":"diuretic-response","display_name":"Renal response to loop diuretics","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"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/chloride-research/27335120.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3\", \"start_char\": 0, \"end_char\": 1432, \"text_sha256\": \"0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Clcnk2 knockout and nephron patch clamp","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Gene deletion; furosemide/thiazide responses","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mouse ortholog; not a claim of dietary chloride deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Chloride research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"chloride","display_name":"Chloride","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A transporter defect changed how two diuretic classes worked.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[chloride-p27335120] The ClC-K2 Chloride Channel Is Critical for Salt Handling in the Distal Nephron. 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