Two murine GSTpi genes are arranged in tandem and are differentially expressed

An 8-kilobase mouse genomic fragment containing two intact glutathione S-transferase (GST) genes has been isolated from a mouse lambda genomic library. Each of the genes (designated mGSTpiA and mGSTpiB) is less than 3 kilobases in size and is comprised of seven exons that give rise to a 630-base pair open reading frame encoding 209 amino acids. The deduced amino acid sequences of the gene products differ in only 6 amino acids at positions 10, 11, 89, 104, 106, and 109. These two genes are highly homologous to rat GST-P and to a lesser extent to human GST-pi. Northern blot analysis of mRNAs from a variety of mouse tissues demonstrated that mGSTpiB is ubiquitously expressed, whereas mGST-piA is more selectively expressed in gallbladder, colon, heart, and skeletal muscle. Primer extension analysis revealed four potential transcription start sites in mGST-piB and one in mGSTpiA. Although both genes were expressed in vitro and in vivo only mGSTpiB product metabolized 1-chloro-2,4-dinitrobenzene, a common GST substrate. Further in vitro expression studies of three chimeric mGSTpi genes suggested that one or both of the amino acids at positions 10 and 11 of mouse GSTpi enzymes are important for the enzyme's ability to metabolize 1-chloro-2,4-dinitrobenzene.