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A single loxP site was inserted 5' to exon 3 and a neomycin selection cassette followed by a loxP site was inserted 3' to exon 4 through homologous recombination. The transient expression of Cre-recombinase within the targeted ES cells resulted in the excision of exons 3 and 4 and the neomycin selection gene. Northern blot analysis of total RNA isolated from the brains of homozygous animals demonstrated that no detectable transcript was expressed from this allele. (J:72940)