A loxP site 272 bp upstream of the translation initiation codon was introduced into exon 1 and a loxP-tauGFP FRT-flanked neo cassette was inserted 1 kb into intron 1 via homologous recombination. Heterozygous animals were crossed to an flp recombinase transgenic line for removal of the neo cassette. Subsequent mating to a cre recombinase transgenic line removed exon 1 and part of intron 1 leaving the tauGFP cassette intact. The exon 1 deletion removes the plasma membrane-targeting signal sequence and also brings the tauGFP cassette under the control of the endogenous promoter. RT-PCR analysis confirmed the removal of the signal sequence in gene transcripts from homozygous mutant animals. Immunohistochemistry of brain sections from homozygous mutants did not detect protein product. (J:76686)