Springer Online Journal Archives 1860-2000
Abstract The human alanine:glyoxylate aminotransferase gene (AGXT) has been cloned and characterized in detail, and various mutant alleles have been shown to be responsible for primary hyperoxaluria type 1 (PH1). However, advances in understanding the basic mechanisms of this rare human disease have been hampered by the lack of a suitable animal model. Although several AGXT homologous genes have been cloned in a number of mammalian species, none of them allows the level of genetic experimentation that current methods provide for mouse embryo manipulation. 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. The full-length mouse Agxt1 cDNA is 1545 bp long, and encodes a 414 amino acid protein. Mouse Agxt1 is highly similar to its rat counterpart both at the nucleotide (91% identity) and the amino acid (92% identity) levels. Like its rat homologue, the larger mRNA species transcribed encodes a conserved amino terminal end characteristic of AGXT forms known to be targeted to the mitochondria. Mouse Agxt1 expression is restricted to the liver, and in vitro transfection of AGXT(−) cells with the cloned Agxt1 cDNA confers AGXT enzymatic activity. At the genomic level, mouse Agxt1 contains 11 exons, spannig 11 Kb, and it maps to the central portion of chromosome 1, a region of known synteny with human distal 2q, where AGXT has been previously mapped (2q36–37).
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