MICE LACKING ORNITHINE-DELTA-AMINO-TRANSFERASE HAVE PARADOXICAL NEONATAL HYPOORNITHINAEMIA AND RETINAL DEGENERATION

Deficiency of ornithine-delta-aminotransferase (OAT) in humans causes hyperornithinaemia and gyrate atrophy (GA), a blinding chorioretinal d egeneration. Surprisingly, OAT-deficient mice produced by gene targeti ng exhibit neonatal hypoornithinaemia and lethality, rescuable by shor t-term arginine supplementation. Post-weaning, these mice develop hype rornithinaemia similar to human GA patients. Subsequent studies in one human GA infant also showed transient hypoornithinaemia. Thus, the OA T reaction plays opposite roles in neonatal and adult mammals. Over se veral months, OAT-deficient mice develop a retinal degeneration with i nvolvement of photoreceptors and pigment epithelium. OAT-deficient mic e appear to be an excellent model of human GA.