Role of Mutation and Pharmacologic Block of @entity9493 ( @entity9678 ) in Vasculogenesis and Fetal Mortality: Partial Rescue by XXXX

@entity1 @entity71894 @entity1970 @entity9493 @entity2533 @entity9678
BACKGROUND: - @entity71894 @entity9678 is a @entity1 missense Long QT2 mutation. Previously we reported that the @entity71894 / @entity71894 mutation embryos disrupted cardiac looping; right ventricle development; and ablated IKr activity at E9.5. The present study evaluates the role of @entity9678 in vasculogenesis. METHODS AND RESULTS: - @entity71894 / @entity71894 yolk sac vessels and aorta consist of sinusoids without normal arborization. Isolated E9.5 +/+ first branchial arches showed normal outgrowth of mERG-positive / @entity1970 co-immunolocalized cells; however outgrowth was grossly reduced in @entity71894 / @entity71894 . @entity71894 / @entity71894 aortas showed fewer @entity1970 positive cells which were not co-immunolocalized with mERG cells. @entity2533 treatment of isolated @entity71894 / @entity71894 embryoid bodies partially rescued this phenotype. Cultured @entity71894 / @entity71894 embryos recapitulate the same cardiovascular phenotypes as seen in vivo. @entity2533 treatment significantly rescued these embryonic phenotypes. Both in vivo and in vitro, dofetilide treatment, over a narrow window of time, entirely recapitulated the @entity71894 / @entity71894 fetal phenotypes. Exogenous @entity2533 treatment also rescued the dofetilide-induced phenotype towards normal. CONCLUSIONS: -Loss of function of @entity9493 results in defects in cardiogenesis and vasculogenesis. Since many medications inadvertently block the @entity9493 potassium current ( @entity9678 ), these novel findings appear to have clinical relevance.
