A loxP site replaced 3 kb of intronic sequence upstream of exon 3 and a floxed neomycin cassette replaced was placed downstream of the exon into a XbaI site. Mice derived from correctly targeted ES cells were crossed with EIIa-cre transgenic mice and progeny were selected by Southern blotting for selective loss of the neomycin resistance cassette. Protein expression was unaffected as determined by immunoblotting of splenocyte extracts. Cre-mediated excision of exon 3 will remove a regulatory domain necessary for proper protein function. (J:144598)