title: Phenotypic characterization of Ggt1(dwg/dwg) mice,a mouse model for hereditary γ-glutamyltransferase deficiency.
abstract: Ggt1(dwg/dwg) mice are spontaneous mutant mice with a nucleotide deletion in the Ggt1 gene. They are characterized by dwarfism, cataract, and coat color abnormality. These abnormalities in the external appearance of Ggt1(dwg/dwg) mice closely resemble those of previously reported GGT1-deficient mice, Ggt1(tm1Zuk/tm1Zuk) (Ggt1(-/-)) and Ggt1(enu1/enu1), generated by gene targeting or ENU mutagenesis. However, whether the pathological features of Ggt1(dwg/dwg) mice are also similar to those of the Ggt1(-/-) and Ggt1(enu1/enu1) mice remains unclear. To clarify the pathogenesis of Ggt1(dwg/dwg) mice, we physiologically and histologically investigated the abnormalities of Ggt1(dwg/dwg) mice in this study. First, we analyzed the activity of GGT1 and GSH levels in Ggt1(dwg/dwg) mice. GGT1 activity in the Ggt1(dwg/dwg) mice was reduced to approximately 4.0% of that in the wild-type mice. Plasma and kidney GSH levels were markedly increased, while eye and liver GSH levels were markedly decreased, in the Ggt1(dwg/dwg) mice. Notably, no significant difference in survival rate was observed between the Ggt1(dwg/dwg) and wild-type mice, whereas high mortality was reported in the Ggt1(-/-) and Ggt1(enu1/enu1) mice. Growth retardation, degeneration of lens fibers, and an increased number of osteoclasts in the Ggt1(dwg/dwg) mice were reversed by administration of N-acetyl-L-cysteine, a precursor of GSH synthesis. Thus, we conclude that the abnormalities of Ggt1(dwg/dwg) mice are caused by alteration of the GSH levels due to the depression of GGT1 activity and that Ggt1(dwg/dwg) mice will be a useful model for GGT deficiency with peculiar features.
authors.affiliation: Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamada
authors.forename: Takehito
authors.initials: T
authors.lastname: Tsuji
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kunieda
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005123:Eye / Q000473:pathology; D017353:Gene Deletion; D018390:Gene Targeting; D005978:Glutathione / Q000378:metabolism*; D006579:Heterozygote; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D005723:gamma-Glutamyltransferase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
chemical_list: D005723:gamma-Glutamyltransferase; D005978:Glutathione