Generating mouse models for studying the function and fate of intrinsic cardiac adrenergic cells.

Embryos lacking the ability to synthesize epinephrine and norepinephrine die (probably due to cardiac failure) without exogenous supplementation while mutant neonates can grow into fertile adults without supplementation. These experiments define a critical period during embryogenesis, when norepinephrine and/or epinephrine are essential for mouse development. The critical period is prior to sympathetic innervation of the heart and prior to synthesis of catecholamines by the adrenal medullae. Recent work indicates that the developing heart is likely to be a major source of catecholamines in the developing mammalian embryo. The spatial pattern of biosynthetic enzymes suggests an association of the intrinsic cardiac adrenergic cells with the developing pacemaker and cardiac conduction cells. To address the functional characteristics and the fate of these cardiac adrenergic cells, we have developed two mouse models that allow us to identify and to characterize the adrenergic cells and their descendants.