Abstract
Gyrate atrophy of the choroid and retina (GACR) is a hereditary form of progressive blindness caused by homozygosity for loss-of-function mutations in the ornithine aminotransferase gene (Oat). The...
Highlights
We used a publically available, auxotrophic Escherichia coli variant to detect and quantify ornithine levels in blood or urine samples taken from mice segregating for inherited defects in ornithine aminotransferase (OAT), an enzyme which in normal adults clears excess ornithine produced in the urea cycle
These mouse mutants, the engineered ornithine aminotransferase gene (Oat) knockout[9] and the spontaneous missense variant called retarded hair growth,[10] have been shown to be excellent models for the inherited human condition known as gyrate atrophy of the choroid and retina (GACR, Online Mendelian Inheritance in Man (OMIM) #258870), which results in visual impairment that begins in childhood with myopia and night blindness and progresses to complete blindness by the fourth or fifth decade of life.[11,12,13]
Escherichia coli strain CAG12185 is an argE mutant and unable to convert glutamate into arginine, a proteinogenic amino acid essential for bacterial growth
Summary
Either naturally occurring or genetically modified, have proven to be useful for detecting and quantifying various analytes in a variety of complex environments,[1,2,3,4,5] including amino acids in physiological fluids that might be diagnostic for certain inherited metabolic disorders.[6,7,8] Here we used a publically available, auxotrophic Escherichia coli variant to detect and quantify ornithine levels in blood or urine samples taken from mice segregating for inherited defects in ornithine aminotransferase (OAT), an enzyme which in normal adults clears excess ornithine produced in the urea cycle (see Figure 1).These mouse mutants, the engineered Oat knockout[9] and the spontaneous missense variant called retarded hair growth,[10] have been shown to be excellent models for the inherited human condition known as gyrate atrophy of the choroid and retina (GACR, Online Mendelian Inheritance in Man (OMIM) #258870), which results in visual impairment that begins in childhood with myopia and night blindness and progresses to complete blindness by the fourth or fifth decade of life.[11,12,13] Dietary restriction of arginine has been shown to prevent (but not reverse) retinal degeneration in OAT-deficient mice.[14]. Because the biosensor system we describe is quantitative, it might be adapted for the routine monitoring of circulating ornithine levels in patients undergoing arginine restriction
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