A targeting construct was designed to insert a loxP site followed by a frt-flanked neomycin (neo) resistance cassette upstream of exon 3 of the methyl CpG binding protein 2 (Mecp2) gene. A second loxP site was inserted in the 3' untranslated region of exon 4. A point mutation was introduced in exon 4, resulting in a missense mutation, A140V, commonly found in humans carrying Rett Syndrome (RTT) X-linked mental retardation. Flp-mediated recombination removed the neo cassette. (J:171410, J:171411)