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A floxed neomycin resistance gene was placed in intron 2 while an additional loxP site was inserted in exon 1. The resulting construct was a hypomorph expressing 80% less mRNA than normal and with a comparable reduction in protein product. Transient transfection of properly targeted ES cells with a cre expression vector to remove neomycin but leaving exon 1 and 2 in place but flanked by loxP sites also resulted in a hypomorph with an identical phenotypic effect. (J:86857)