{"id":"abc8e8ce-c1d3-5c03-bbdf-d825b47d7112","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-loss-causes-myeloproliferation","predicate":"loss_increases","statement":"Conditional Tet2 loss produced progressive enlargement of the haematopoietic stem-cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis and extramedullary haematopoiesis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"f1d38e49-429e-520c-a6a7-9cdeeeea1462","mechanism_event_label":"Conditional Tet2 loss produced progressive enlargement of the haematopoietic stem-cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis and extramedullary haematopoiesis.","subject":{"id":"36d7160b-6534-58a6-a0df-55bcde8e740c","slug":"tet2-mouse","display_name":"Mouse Tet2","entity_type_key":"protein"},"object":{"id":"08c7e043-7fbb-5796-8175-3554fceb5398","slug":"mouse-myeloproliferation","display_name":"Myeloproliferation in mice","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f1d38e49-429e-520c-a6a7-9cdeeeea1462","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-loss-causes-myeloproliferation-event","event_type":"observed_relationship","label":"Conditional Tet2 loss produced progressive enlargement of the haematopoietic stem-cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis and extramedullary haematopoiesis.","description":"Mice without Tet2 went on to develop a blood disorder of overgrowth.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"36d7160b-6534-58a6-a0df-55bcde8e740c","slug":"tet2-mouse","display_name":"Mouse Tet2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"08c7e043-7fbb-5796-8175-3554fceb5398","slug":"mouse-myeloproliferation","display_name":"Myeloproliferation in mice","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":"duration","value_text":"Progressive, in vivo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Conditional Tet2-knockout mice followed in vivo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Conditional genetic deletion of Tet2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Myeloproliferation in a conditional knockout mouse is not the same entity as a human myelodysplastic syndrome, and this model deletes the gene rather than reproducing a point mutation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Mice without Tet2 went on to develop a blood disorder of overgrowth.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[moran-crusio-2011] Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation (2011). https://pubmed.ncbi.nlm.nih.gov/21723200/ DOI: 10.1016/j.ccr.2011.06.001","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Bone marrow, spleen and peripheral blood","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":"c0aaa0b1-ac81-5e1b-a9dd-5404c58cb179","evidence_kind":"source_excerpt","locator":"Lines 63-71","start_line":63,"end_line":71,"excerpt":"## tet2-loss-causes-myeloproliferation\nConditional Tet2 loss produced progressive enlargement of the haematopoietic stem-cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis and extramedullary haematopoiesis.\nModel/species: Conditional Tet2-knockout mice followed in vivo\nOrganism: Mus musculus\nTissue/system: Bone marrow, spleen and peripheral blood\nExposure: Conditional genetic deletion of Tet2\nDuration: Progressive, in vivo\nLimits: Myeloproliferation in a conditional knockout mouse is not the same entity as a human myelodysplastic syndrome, and this model deletes the gene rather than reproducing a point mutation.\nPrimary reference: [moran-crusio-2011] Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation (2011). https://pubmed.ncbi.nlm.nih.gov/21723200/ DOI: 10.1016/j.ccr.2011.06.001","model_system":"Conditional Tet2-knockout mice followed in vivo","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c0b9b176-985b-55c7-b8f5-f3ca16a7ddfe","stable_key":"import-a2968a2f-5b00-5212-8b8c-8a4262bcb149","title":"TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies located by Europe PMC title search, with every statement drafted from the retrieved abstract. Two pairs share a laboratory and are recorded as one line of evidence each. Genetic loss of function, pharmacological exposure and dietary depletion are kept as separate record types. Not publisher full text.","file_path":"","sha256":"22e2c8388d4f0c1813546ba6a9ccee3fa14c0c8f578bd9bd80103c1390b2536b","revision_id":"fbc29d8d-0420-562c-bfdb-1b5af42f2d08","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}