To unravel the complex disease phenotype of @entity712 , we are utilizing an integrative approach employing genomics, physiology, and @entity19 genetics to identify nodal pathways for specific physiological end points such as myocyte stretch activation responses, contractility and electrical conduction. A new class of genetic pathways for @entity1164 and associated @entity943 has been based on transcription factors that control conduction system lineages, including @entity69211 / @entity69211 and @entity39756 . Previous studies have established that @entity69211 plays a critical role in conduction system lineage formation and the loss of @entity69211 leads to a confused electrophysiological identity in Purkinje and ventricular cell lineages, resulting in @entity1164 and marked tachy and @entity943 . Utilizing @entity69211 and @entity39756 floxed alleles, we now have identified the primary pathways which link these transcription factors with cardiac arrythmogenesis. @entity19 which harbour a neural crest restricted knockout of @entity69211 display marked arrhythmogenesis and conduction system defects, implicating neural crest cues in conduction system development and disease. @entity19 which harbour a ventricular-restricted knockout of @entity39756 display completely normal conduction at birth, but a hypoplastic atrioventricular (AV) node. During maturation, progressive @entity616 ensues, associated with a selective dropout of distal AV nodal cell lineages at the boundaries of the penetrating His bundle. Single cell analyses examining individual nodal cells within AV node of ventricular restricted @entity39756 knockout @entity19 clearly document a cell autonomous requirement for @entity39756 within AV nodal lineages per se. Micro-electrophysiological AV nodal mapping indicates a selective conduction defect at the boundary of the distal AV node and His bundle. @entity69211 and @entity39756 reflect new cardiac cell non-autonomous and autonomous pathways for conduction system lineage defects and associated cardiac arrythmogenesis.

Defects in cardiac conduction system lineages and malignant XXXX : developmental pathways and disease.

@entity1164 :: ('MESH:D016757', 'Disease') :: ['cardiac sudden death'] @entity39756 :: ('18091(Tax:10090)', 'Gene') :: ['NKX2.5', 'Nkx2.5'] @entity712 :: ('MESH:D006333', 'Disease') :: ['heart failure'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse', 'Mice'] @entity69211 :: ('20688(Tax:10090)', 'Gene') :: ['Hf1b', 'HF1b', 'SP4'] @entity943 :: ('MESH:D001145', 'Disease') :: ['arrhythmias', 'brady arrhythmias'] @entity616 :: ('MESH:D006327', 'Disease') :: ['complete heart block']
@entity943 :: (MESH:D001145,Disease) :: ['arrhythmias']
