Mice lacking ornithine-delta-aminotransferase have paradoxical neonatal hypoornithinaemia and retinal degeneration.
Deficiency of ornithine-delta-aminotransferase (OAT) in humans causes hyperornithinaemia and gyrate atrophy (GA), a blinding chorioretinal degeneration. Surprisingly, OAT-deficient mice produced by gene targeting exhibit neonatal hypoornithinaemia and lethality, rescuable by short-term arginine supplementation. Post-weaning, these mice develop hyperornithinaemia similar to human GA patients. Subsequent studies in one human GA infant also showed transient hypoornithinaemia. Thus, the OAT reaction plays opposite roles in neonatal and adult mammals. Over several months, OAT-deficient mice develop a retinal degeneration with involvement of photoreceptors and pigment epithelium. OAT-deficient mice appear to be an excellent model of human GA.
Wang
T
T
Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, USA.
Lawler
A M
AM
Steel
G
G
Sipila
I
I
Milam
A H
AH
Valle
D
D
D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000378:metabolism; D001483:Base Sequence; D017931:DNA Primers; D005527:Food, Fortified; D005838:Genotype; D015799:Gyrate Atrophy / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D008239:Lysine / Q000097:blood; D008322:Mammals; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009952:Ornithine / Q000097:blood / Q000378:metabolism*; D009953:Ornithine-Oxo-Acid Transaminase / Q000172:deficiency* / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers; D001120:Arginine; D009952:Ornithine; D009953:Ornithine-Oxo-Acid Transaminase; D008239:Lysine