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Transgenic and Gene Knockout Analysis of Diabetic Neuropathy

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Diabetic Neuropathy

Part of the book series: Clinical Diabetes ((CLD))

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Abstract

Neuropathy is one of the major complications of long-term diabetes. Despite many years of intense research by a number of laboratories, the pathogenetic mechanisms of this disease are still not completely understood. Likely contributing factors of this disease include the polyol pathway, nonenzymatic glycation, protein kinase-C activation, hexosamine pathway, and overproduction of superoxide by the mitochondrial respiratory chain. Their roles in the pathogenesis of diabetic neuropathy are mainly supported by pharmacological studies, which often have inherent problem of uncertain drug specificity and availability. This article reviews the recent studies using transgenic and gene knockout mice to examine the role of polyol pathway, nonenzymatic glycation, poly(adenosine 5′-diphosphate [ADP]-ribose) polymerase, and neurofilaments in diabetic neuropathy. The results of these studies confirm some of the findings from drug experiments and also settle some controversies. These genetic studies avoid some of the problems of using chemical inhibitors, but they also have inherent problems of their own. The prospect of using more sophisticated inducible transgene expression, and conditional gene ablation technologies to circumvent these problems are discussed. It is expected that the number of genetically engineered mutant mice will increase exponentially in the near future and some of them will undoubtedly contribute to our understanding of diabetic neuropathy.

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Authors and Affiliations

  1. Department of Anatomy, The University of Hong Kong, Hong Kong, SAR China

    Sookja K. Chung

  2. Department of Physiology, The University of Hong Kong, Hong Kong, SAR China

    Stephen S. M. Chung

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  1. Sookja K. Chung
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  2. Stephen S. M. Chung
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Editors and Affiliations

  1. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

    Aristidis Veves MD, DSc

  2. Manchester Royal Infirmary and University of Manchester, Manchester, UK

    Rayaz A. Malik MBChB, PhD

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© 2007 Humana Press Inc., Totowa, NJ

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Chung, S.K., Chung, S.S.M. (2007). Transgenic and Gene Knockout Analysis of Diabetic Neuropathy. In: Veves, A., Malik, R.A. (eds) Diabetic Neuropathy. Clinical Diabetes. Humana Press. https://doi.org/10.1007/978-1-59745-311-0_4

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  • DOI: https://doi.org/10.1007/978-1-59745-311-0_4

  • Publisher Name: Humana Press

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