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Mice lacking ornithine–δ–amino–transferase have paradoxical neonatal hypoornithinaemia and retinal degeneration

Nature Genetics volume 11, pages 185–190 (1995)Cite this article

Abstract

Deficiency of ornithine–δ–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.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2185, USA

    Tao Wang, Gary Steel & David Valle

  2. Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2185, USA

    Tao Wang & David Valle

  3. Department of Obstetrics and Gynecology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2185, USA

    Ann M. Lawler

  4. Department of Pediatrics, Aurora Hospital, Helsinki, Finland

    Ilkka Sipila

  5. Department of Ophthalmology, University of Washington School of Medicine, Seattle, Washington, 98195-6485, USA

    Ann H. Milam

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  1. Tao Wang
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  2. Ann M. Lawler
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  6. David Valle
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Wang, T., Lawler, A., Steel, G. et al. Mice lacking ornithine–δ–amino–transferase have paradoxical neonatal hypoornithinaemia and retinal degeneration. Nat Genet 11, 185–190 (1995). https://doi.org/10.1038/ng1095-185

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