In ES cells carrying the Nprl3 allele, Hba erythroid-specific enhancer R3 in Nprl3 intron 2 was replaced with a loxP site flanked neomycin resistance gene cassette. Subsequent cre-mediated recombination removed the neo cassette and the 12402 bp span between the loxP site in place of Nprl3 promoter P6 (Rr246493) and enhancer R3 (Rr351), which also serves as a promoter for Nprl3 transcripts with alternative, more downstream, 1st exons. The deletion also includes putative Hba enhancer Rm or DHS-12 (Rr352) in Nprl3 intron 1 and Nprl3 exons 1 and 2. RNA-FISH analysis indicates Nprl3 expression is eliminated in the brain but not in erythroid cells. Expression in erythroid cells from homozygous mice is about 20% that of wild-type, presumably from alternatively spliced transcripts with alternative 1st exons. No protein expression was detected in any tissue. (J:184965)