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Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria

Nature Genetics volume 12, pages 195–199 (1996)Cite this article

Abstract

Acute Intermittent porphyria (AIP) is a human disease resulting from a dominantly inherited partial deficiency of the heme biosynthetic enzyme, porphobilinogen deaminase (PBGD)1–3. The frequency of the trait for AIP is 1/10,000 in most populations, but may be markedly higher (1/500) in psychiatric patients1,4. The clinical expression of the disease is characterized by acute, life-threatening attacks of ‘porphyric neuropathy’ that include abdominal pain, motor and sensory neurological deficits and psychiatric symptoms1. Attacks are frequently precipitated by drugs, alcohol and low caloric intake. Identical symptoms occur in other hepatic porphyrias. To study the pathogenesis of the neurologic symptoms of AIP we have generated Pbgd-deficient mice by gene targeting. These mice exhibit the typical biochemical characteristics of human AIP, notably, decreased hepatic Pbgd activity, increased δ-aminolevulinic acid synthase activity and massively increased urinary excretion of the heme precursor, δ-aminolevulinic acid after treatment with drugs such as phenobarbital. Behavioural tests reveal decreased motor function and-histo-pathological findings include axonal neuropathy and neurologic muscle atrophy.

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Authors and Affiliations

  1. Department of Pharmacology, Biozentrum, University of Basel, CH-4056, Basel, Switzerland

    Raija L.P. Lindberg & Urs A. Meyer

  2. Inserm U409, Faculty X. Bichat, F-75018, Paris, France

    Catherine Porcher & Bernard Grandchamp

  3. Predinical Research, Sandoz Pharma Ltd., CH-4002, Basel, Switzerland

    Birgit Ledermann & Kurt Bürki

  4. Institute of Neuropathology, University Hospital, CH-8091, Zurich, Switzerland

    Sebastian Brandner & Adriano Aguzzi

Authors
  1. Raija L.P. Lindberg
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  8. Urs A. Meyer
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Lindberg, R., Porcher, C., Grandchamp, B. et al. Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria. Nat Genet 12, 195–199 (1996). https://doi.org/10.1038/ng0296-195

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