ERV-3 envelope expression and congenital heart block: What does a physiological knockout teach us

Congenital heart block is a serious condition with significant mortality du e in most cases to the transplacental transfer of autoantibodies from an ot herwise asymptomatic mother. Although SSA/Ro and SSB/La autoantibodies have been implicated, attention has focused recently on autoantibodies to envel ope proteins of endogenous retrovirus-3 (ERV-3), We have recently described a natural knock out model for ERV-3 involving severely truncated form of t he protein due to a premature stop mutation. If a pregnant female homozygous for the truncated form of the ERV-3 carries a foetus expressing the entire protein, the mother might be expected to ac quire high titre immunity, while the foetus homozygous for the truncated fo rm would not be expected to immunise its mother. In order to test whether t his naturally occurring model could shed light on the ETO pathogenesis of C HB, we tested the ERV-3 stop polymorphism's in the mothers of 12 CHB infant s, but not was homozygous for the stop mutation. These data tend to rule ou t a role for the stop polymorphism in the generation of antibodies to ERV-3 during pregnancy, but not that other polymorphism's might be responsible.