IngentaConnect Characteristics of murine histidinaemia and its potential for gen...

Authors: N. Mellor¹; M. Themis²; C. Selden¹; M. Jones³; H. J. F. Hodgson¹

Source: Liver International, Volume 24, Number 4, August 2004 , pp. 354-360(7)

Abstract:

Mellor N, Themis M, Selden C, Jones M, Hodgson HJF. Characteristics of murine histidinaemia and its potential for genetic manipulation.

Liver International 2004: DOI: 10.1111/j.1478-3231.2004.0929.x. © Blackwell Munksgaard 2004 Abstract: Background:

Histidinaemia is an autosomal recessive disorder affecting the hepatic enzyme histidine ammonia lyase (histidase) resulting in elevated plasma and urinary histidine and is prototypic of a series of hepatic cytosolic enzyme defects. Aims:

To characterise the physiology of murine histidinaemia with respect to histidine excretion and catabolism, and explore the potential for manipulating cellular and whole body histidase metabolism by gene transfer. Materials and Methods:

We studied his/his mice which have a G to A substitution in the gene encoding histidase, using both in vitro transduction of isolated hepatocytes by lipofection with wild-type histidase cDNA, and in vivo transduction of whole liver using a retroviral construct. Results and Conclusion:

Histidase cDNA expression restored histidase activity in vivo and in vitro towards normal levels, demonstrated both at the cellular level and by whole body metabolic studies, establishing the potential of this model for the development of new gene therapeutic approaches.

Keywords: histidase; histidinaemia; liver

Document Type: Research article

DOI: 10.1111/j.1478-3231.2004.0929.x

Affiliations: 1: Centre for Hepatology, Department of Medicine, Royal Free and University College School of Medicine, London, UK 2: Cystic Fibrosis Gene Therapy Research Group, Department of Biomedical Sciences, Imperial College School of Medicine, London, UK 3: Department of Infectious Diseases, Hammersmith Campus, Imperial College School of Medicine, London, UK

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