A 1312 bp sequence containing the Hba erythroid regulatory element (HS -26), located in Nprl3 intron 4 and containing transcription factor binding elements for the hemoglobin alpha genes, was replaced with a loxP site flanked neomycin resistance gene cassette. Expression of the Nprl3 gene was severely down-regulated although the open reading frame of the gene was not disrupted. (J:80121)