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Gene Review

Agxt  -  alanine-glyoxylate aminotransferase

Mus musculus

Synonyms: AGT, Agt1, Agxt1, Alanine--glyoxylate aminotransferase, SPT, ...
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Disease relevance of Agxt

  • Application of this procedure in a recently developed Agxt-gene-deleted mouse model of PH1 resulted in marked amelioration of hyperoxaluria [1].
  • This inhibition was overridden by coapplications of ceramides (the distal SPT product), indicating that the delay in repair was not due to non-specific toxicity [2].
  • Alanine-glyoxylate aminotransferase-deficient mice, a model for primary hyperoxaluria that responds to adenoviral gene transfer [3].
  • Our data also suggest that hyperinsulinemia and elevated tumor necrosis factor (TNF)-alpha associated with obesity may contribute to the observed increase in adipose NSMase, ASMase, and SPT mRNA in this murine model of obesity [4].
  • This study showed that children with high-grade glioma have an innate resistance to alkylating agents based on mismatch repair deficiency and high levels of alkyguanine transferase (AGT) [5].

High impact information on Agxt

  • We generated a null mutant mouse by targeted mutagenesis of the homologous gene, Agxt, in embryonic stem cells [3].
  • Hepatic expression of human AGT1, the protein encoded by AGXT, by adenoviral vector-mediated gene transfer in Agxt(-/-) mice normalized urinary oxalate excretion and prevented oxalate crystalluria [3].
  • Expression of enzymes involved in ceramide generation (neutral sphingomyelinase [NSMase], acid sphingomyelinase [ASMase], and serine-palmitoyl-transferase [SPT]) and ceramide hydrolysis (ceramidase) are elevated in obese adipose tissues [4].
  • To investigate the relationship between sphingolipid metabolism and atherosclerosis, we utilized myriocin to inhibit mouse serine palmitoyl-CoA transferase (SPT), the key enzyme for sphingolipid biosynthesis [6].
  • These results indicate that, apart from cholesterol levels, sphingolipids have an effect on atherosclerotic development and that SPT has proatherogenic properties [6].

Biological context of Agxt

  • The mouse alanine:glyoxylate aminotransferase gene (Agxt1): cloning, expression, and mapping to chromosome 1 [7].

Associations of Agxt with chemical compounds

  • On a chow diet, myriocin treatment caused a significant decrease (50%) in liver SPT activity (p < 0.001), significant decreases in plasma sphingomyelin, ceramide, and sphingosine-1-phosphate levels (54, 32, and 73%, respectively) (p < 0.0001), and a significant increase in plasma phosphatidylcholine levels (91%) (p < 0.0001) [6].
  • Mice that lack AGT in all organs, O(6)-methylguanine-DNA methyltransferase gene knockout (MGMT(-/-)) mice are extremely hypersensitive to the methylating agent N-methyl-N-nitrosourea (MNU) and exhibit a 10-fold reduction in the LD(90) [8].

Analytical, diagnostic and therapeutic context of Agxt

  • Thus, we have carried out the molecular cloning and analysis of the mouse Agxt1 gene, as a necessary first step towards the generation of a mouse model for PH1 [7].


  1. Feasibility of hepatocyte transplantation-based therapies for primary hyperoxalurias. Guha, C., Yamanouchi, K., Jiang, J., Wang, X., Roy Chowdhury, N., Santana, A., Shapiro, L.J., Salido, E., Roy-Chowdhury, J. American journal of nephrology. (2005) [Pubmed]
  2. Sphingolipids are required for mammalian epidermal barrier function. Inhibition of sphingolipid synthesis delays barrier recovery after acute perturbation. Holleran, W.M., Man, M.Q., Gao, W.N., Menon, G.K., Elias, P.M., Feingold, K.R. J. Clin. Invest. (1991) [Pubmed]
  3. Alanine-glyoxylate aminotransferase-deficient mice, a model for primary hyperoxaluria that responds to adenoviral gene transfer. Salido, E.C., Li, X.M., Lu, Y., Wang, X., Santana, A., Roy-Chowdhury, N., Torres, A., Shapiro, L.J., Roy-Chowdhury, J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Altered adipose and plasma sphingolipid metabolism in obesity: a potential mechanism for cardiovascular and metabolic risk. Samad, F., Hester, K.D., Yang, G., Hannun, Y.A., Bielawski, J. Diabetes (2006) [Pubmed]
  5. A phase II window trial of procarbazine and topotecan in children with high-grade glioma: a report from the children's oncology group. Chintagumpala, M.M., Friedman, H.S., Stewart, C.F., Kepner, J., McLendon, R.E., Modrich, P.L., McCluggage, C., Burger, P., Holmes, E., Thompson, S., Rutka, J., Michalski, J., Woo, S., Blaney, S.M., Kun, L.E., Horowitz, M.E. J. Neurooncol. (2006) [Pubmed]
  6. Effect of myriocin on plasma sphingolipid metabolism and atherosclerosis in apoE-deficient mice. Hojjati, M.R., Li, Z., Zhou, H., Tang, S., Huan, C., Ooi, E., Lu, S., Jiang, X.C. J. Biol. Chem. (2005) [Pubmed]
  7. The mouse alanine:glyoxylate aminotransferase gene (Agxt1): cloning, expression, and mapping to chromosome 1. Li, X.M., Salido, E.C., Shapiro, L.J. Somat. Cell Mol. Genet. (1999) [Pubmed]
  8. MGMT expression in murine bone marrow is a major determinant of animal survival after alkylating agent exposure. Reese, J.S., Qin, X., Ballas, C.B., Sekiguchi, M., Gerson, S.L. J. Hematother. Stem Cell Res. (2001) [Pubmed]
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