title: Mice lacking three Loci encoding 14 glutathione transferase genes: a novel tool for assigning function to the GSTP, GSTM, and GSTT families.
abstract: Glutathione S-transferases (GSTs) form a superfamily defined by their ability to catalyze the conjugation of glutathione with electrophilic substrates. These enzymes are proposed to play a critical role in protection of cellular components from damage mediated by reactive metabolites. Twenty-two cytosolic GSTs, grouped into seven families, are recognized in mice. This complexity hinders the assignment of function to a subset or family of these genes. We report generation of a mouse line in which the locus encoding three GST gene families is deleted. This includes the four Gstt genes spanning 65 kb on chromosome 10 and the seven Gstm genes found on a 150 kb segment of DNA chromosome 3. In addition, we delete two Gstp genes on chromosome 19 as well as a third related gene located 15 kb telomeric to Gstp1 and Gstp2, which we identify as a potential new member of this gene family. We show that, despite the loss of up to 75% of total GST activity in some tissues from these animals, the mice are healthy and fertile, with normal life expectancy. The normal development and health of these animals make them an appropriate model for defining the role of these families in redox homeostasis and metabolism of drugs and environmental pollutants.
authors.affiliation: Department of Genetics (Z.X., J.N.S., M-T.N., P.W.R., A.M.L., J.M.C., B.H.K.), and Pulmonary and Critical Care Division, Department of Medicine (M.K., B.H.K.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Xiang
authors.forename: John N
authors.initials: JN
authors.lastname: Snouwaert
authors.forename: Martina
authors.initials: M
authors.lastname: Kovarova
authors.forename: Mytrang
authors.initials: M
authors.lastname: Nguyen
authors.forename: Peter W
authors.initials: PW
authors.lastname: Repenning
authors.forename: Anne M
authors.initials: AM
authors.lastname: Latour
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Cyphert
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Koller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D051549:Glutathione S-Transferase pi / Q000172:deficiency / Q000235:genetics*; D005982:Glutathione Transferase / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496557:Gstp1 protein, mouse