This report describes primary hyperoxaluria, type 1 (HP1 pr PH1), which is a subtype of primary hyperoxaluria; HP1 exhibits autosomal recessive inheritance. The human gene implicated in this disease is AGXT, a liver peroxisomal enzyme that catalyzes the conversion of glyoxylate to glycine. There is a single orthologous gene in Drosophila, Agxt, for which RNAi-targeting constructs have been generated.
The human AGXT gene has not been introduced into flies.
The Malpighian tubules of wild-type animals and animals in which ubiquitous knockdown of Dmel\Agxt was effected by RNAi were examined and compared for crystal formation; energy dispersive X-ray spectroscopy (EDS) was used to identify the chemical composition of detected crystals. On a normal diet, the Agxt-knockdown, but not the wild-type, animals developed calcium oxalate crystals; on a diet supplemented with sodium oxalate, both groups developed crystals. This system has been used to assess the efficacy of therapeutic options.
[updated Feb. 2019 by FlyBase; FBrf0222196]
Primary hyperoxaluria is characterized by an accumulation of nonsoluble calcium oxalate in various bodily tissues, especially the kidney, resulting in renal failure. [from MIM:259900; 2019.02.14]
[HYPEROXALURIA, PRIMARY, TYPE I; HP1](https://omim.org/entry/259900)
[ALANINE-GLYOXYLATE AMINOTRANSFERASE; AGXT](https://omim.org/entry/604285)
Type I primary hyperoxaluria (HP1) is caused by homozygous or compound heterozygous mutation in the gene encoding alanine-glyoxylate aminotransferase (AGXT). [from MIM:259900; 2019.02.14]
The AGXT gene is expressed only in the liver and the encoded protein is localized mostly in the peroxisomes, where it is involved in glyoxylate detoxification. [Gene Cards, AGXT; 2019.02.14]
Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver peroxisomal enzyme alanine:glyoxylate-aminotransferase (AGT), which catalyzes the conversion of glyoxylate to glycine. When AGT activity is absent, glyoxylate is converted to oxalate, which forms insoluble calcium oxalate crystals that accumulate in the kidney and other organs. [Gene Reviews, Primary Hyperoxaluria Type 1; 2019.02.14]
Affected individuals have decreased or absent AGXT activity and a failure to transaminate glyoxylate, which causes the accumulated glyoxylate to be oxidized to oxalate. [from MIM:259900; 2019.02.14]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human AGXT (1 Drosophila to 1 human). Dmel\Agxt shares 46% identity and 63% similarity with the human gene.
