A portion of exon 2 was replaced by a neomycin selection cassette inserted by homologous recombination. The deleted region encoded transmembrane domains 6 and 7 (amino acids 217 through 275). Two aberrant transcripts were detected in mutant mice by Northern blot and RT-PCR analyses. Analysis indicated that a 613 bp transcript resulted from readthrough of the neo cassette and a 380 bp transcript underwent splicing of codon 198 to exon 3. Biochemical analysis, based on pH recover after an acute acid load, of acinar cells indicated a functional ablation of the endogenous protein. (J:54705)