Phenotypic characterization of ggt1dwg/dwg mice, a mouse model for hereditary γ-glutamyl transferase deficiency

Kaoru Yamada, Takehito Tsuji, Tetsuo Kunieda

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Ggt1dwg/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 Ggt1dwg/dwg mice closely resemble those of previously reported GGT1-deficient mice, Ggt1tm1Zuk/tm1Zuk (Ggt1-/-) and Ggt1enu1/enu1, generated by gene targeting or ENU mutagenesis. However, whether the pathological features of Ggt1dwg/dwg mice are also similar to those of the Ggt1-/- and Ggt1enu1/enu1 mice remains unclear. To clarify the pathogenesis of Ggt1dwg/dwg mice, we physiologically and histologically investigated the abnormalities of Ggt1dwg/dwg mice in this study. First, we analyzed the activity of GGT1 and GSH levels in Ggt1dwg/dwg mice. GGT1 activity in the Ggt1dwg/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 Ggt1dwg/dwg mice. Notably, no significant difference in survival rate was observed between the Ggt1dwg/dwg and wild-type mice, whereas high mortality was reported in the Ggt1-/- and Ggt1enu1/enu1 mice. Growth retardation, degeneration of lens fibers, and an increased number of osteoclasts in the Ggt1dwg/dwg mice were reversed by administration of N-acetyl-L-cysteine, a precursor of GSH synthesis. Thus, we conclude that the abnormalities of Ggt1dwg/dwg mice are caused by alteration of the GSH levels due to the depression of GGT1 activity and that Ggt1dwg/dwg mice will be a useful model for GGT deficiency with peculiar features.

Original languageEnglish
Pages (from-to)151-157
Number of pages7
JournalExperimental Animals
Volume62
Issue number2
DOIs
Publication statusPublished - May 1 2013

Keywords

  • Ggt1
  • Glutathione
  • Mouse
  • Mutation

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Biochemistry, Genetics and Molecular Biology(all)
  • veterinary(all)

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