PHYSIOLOGICAL KNOCKOUT OF THE ENVELOPE GENE OF THE SINGLE-COPY ERV-3 HUMAN ENDOGENOUS RETROVIRUS IN A FRACTION OF THE CAUCASIAN POPULATION

ERV-3 is an evolutionarily conserved single-copy human endogenous retr ovirus with a coding envelope gene potentially involved in important p lacental functions. We have investigated the sequence variability of t his gene among 150 unrelated Caucasian individuals and found eight pol ymorphic sites. One of them corresponds to the introduction of a stop codon resulting in the production of a severely truncated ERV-3 envelo pe protein lacking both the fusion peptide and the immunosuppressive d omain of the protein. The stop codon is observed in a homozygous state in approximately 1% of Caucasian individuals without evidence for cou nterselection, thus precluding the involvement of any essential functi on of the gene in placental implantation and development. This natural knockout provides a mean to investigate other potential roles for thi s otherwise highly conserved gene.