Agxt KO Mice

Catalog Number: C001703

Strain Name: C57BL/6NCya-Agxtem1/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

Strain Description

The AGXT gene, mapping to chromosome 2q37.3, encodes alanine-glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate-dependent homotetrameric enzyme predominantly expressed in hepatic peroxisomes [1]. AGT is central to glyoxylate metabolism, catalyzing its transamination to glycine and preventing its oxidation to oxalate [1]. Primary Hyperoxaluria Type 1 (PH1), a rare autosomal recessive disorder affecting approximately 1-3 per million individuals, arises from over 175 identified pathogenic mutations in AGXT. These mutations typically result in deficient or mislocalized AGT, leading to marked overproduction of oxalate [2]. The ensuing hyperoxaluria causes deposition of calcium oxalate in the kidneys, manifesting as nephrolithiasis and nephrocalcinosis, which can progress to end-stage renal disease [3]. In severe cases, systemic oxalosis can occur [4]. Agxt-deficient mice serve as critical preclinical models, faithfully mirroring the biochemical and pathological features of PH1 and enabling the evaluation of diverse therapeutic modalities, including enzyme replacement, substrate reduction, and gene therapy.

The Agxt KO mouse is a gene knockout model created using gene-editing techniques to knock out the coding sequence of the Agxt gene (the homolog of the human AGXT gene) in mice. This model is used to research the pathogenic mechanisms of primary hyperoxaluria and develop related therapeutic strategies.

 

Strain Strategy

The mouse Agxt gene in mice consists of 11 exons, with the start codon in exon 1 and the stop codon in exon 11. This strain was created by gene-editing techniques that knocked out the region spanning exons 3 ~ 8.


Application

  • Studies of glyoxylate metabolism regulation;
  • Primary Hyperoxaluria pathogenesis and therapeutic drug evaluation;

 

Validation Data

1. Urine biochemical indexes


Figure 1. Urine biochemical analysis of Agxt KO and wild-type mice. Twelve-week-old male mice were administered 0.7% ethylene glycol (EG) in their drinking water for three weeks to induce the production of a toxic metabolite (oxalate). The results showed that urinary oxalic acid (Urine Oxalic), microalbuminuria (mALB), and urine albumin/creatinine ratio (Urine UACR) were significantly elevated in Agxt KO mice compared to wild-type (WT) mice. These data indicate that the absence of alanine-glyoxylate aminotransferase (AGT), which is closely related to the metabolism of oxalate precursors, leads to impaired renal function in Agxt KO mice.

 

2. Renal H&E Staining


Figure 2. Renal H&E staining of homozygous male Agxt KO and wild-type mice after ethylene glycol (EG) induction (male, 15 weeks old). The results revealed pathological changes in the kidney tissue of Agxt KO mice compared to wild-type mice, primarily characterized by renal tubular dilation with mild severity (affecting less than 10% of the tissue area).

 

References
[1]Williams EL, Acquaviva C, Amoroso A, Chevalier F, Coulter-Mackie M, Monico CG, Giachino D, Owen T, Robbiano A, Salido E, Waterham H, Rumsby G. Primary hyperoxaluria type 1: update and additional mutation analysis of the AGXT gene. Hum Mutat. 2009 Jun;30(6):910-7.
[2]Sun Y, Li W, Shen S, Yang X, Lu B, Zhang X, Lu P, Shen Y, Ji J. Loss of alanine-glyoxylate and serine-pyruvate aminotransferase expression accelerated the progression of hepatocellular carcinoma and predicted poor prognosis. J Transl Med. 2019 Nov 26;17(1):390.
[3]Soliman NA, Mabrouk S. Primary hyperoxaluria type 1 in developing countries: novel challenges in a new therapeutic era. Clin Kidney J. 2022 May 17;15(Suppl 1):i33-i36.
[4]Gang X, Liu F, Mao J. Lumasiran for primary hyperoxaluria type 1: What we have learned? Front Pediatr. 2023 Jan 10;10:1052625.