Animal models of Wilson disease

Valentina Medici, Dominik Huster

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Citations (Scopus)

Abstract

Wilson disease (WD) is caused by ATPase copper-transporting beta (ATP7B) mutations and results in copper toxicity in liver and brain. Although the defective gene was identified in 1993, the specific mechanisms underlying copper toxicity and the remarkable phenotypic diversity of the disease are still poorly understood. Animal models harboring defects in the ATP7B homolog have helped to reveal new insights into pathomechanisms of WD. Four rodent models with ATP7B gene defects have been described – the Long–Evans Cinnamon (LEC) rat, inbred mouse models (toxic milk (tx), the Jackson Laboratory toxic milk (tx-j)), and the genetically engineered ATP7B–/– (knockout) mouse – all of which develop liver disease to different extents. Copper accumulation in parts of the brain accompanied by some neurologic involvement was revealed in LEC rats and tx/tx-j mice, but the pathology is less severe than human neurologic WD. Several dogs show hepatic copper toxicity resembling WD; however, brain involvement has not been observed and the underlying genetic defect is different. These models are of great value for examination of copper distribution and metabolism, gene expression, and investigation of liver and brain pathology. The availability of disease models is essential for therapeutic interventions such as drug, gene, and cell therapy. Findings made by animal studies may facilitate the development of specific therapies to ameliorate WD progression.

Original languageEnglish (US)
Title of host publicationHandbook of Clinical Neurology
PublisherElsevier B.V.
Pages57-70
Number of pages14
Volume142
DOIs
StatePublished - 2017

Publication series

NameHandbook of Clinical Neurology
Volume142
ISSN (Print)00729752
ISSN (Electronic)22124152

Fingerprint

Hepatolenticular Degeneration
Copper
Animal Models
Cinnamomum zeylanicum
Poisons
Brain
Liver
Milk
Pathology
Cell- and Tissue-Based Therapy
Nervous System Diseases
Knockout Mice
Genetic Therapy
Nervous System
Genes
Disease Progression
Liver Diseases
Rodentia
Dogs
Gene Expression

Keywords

  • animal model
  • ATP7B
  • brain
  • copper toxicity
  • inherited disease
  • liver
  • metabolism
  • Wilson disease

ASJC Scopus subject areas

  • Medicine(all)
  • Neurology
  • Clinical Neurology

Cite this

Medici, V., & Huster, D. (2017). Animal models of Wilson disease. In Handbook of Clinical Neurology (Vol. 142, pp. 57-70). (Handbook of Clinical Neurology; Vol. 142). Elsevier B.V.. https://doi.org/10.1016/B978-0-444-63625-6.00006-9

Animal models of Wilson disease. / Medici, Valentina; Huster, Dominik.

Handbook of Clinical Neurology. Vol. 142 Elsevier B.V., 2017. p. 57-70 (Handbook of Clinical Neurology; Vol. 142).

Research output: Chapter in Book/Report/Conference proceedingChapter

Medici, V & Huster, D 2017, Animal models of Wilson disease. in Handbook of Clinical Neurology. vol. 142, Handbook of Clinical Neurology, vol. 142, Elsevier B.V., pp. 57-70. https://doi.org/10.1016/B978-0-444-63625-6.00006-9
Medici V, Huster D. Animal models of Wilson disease. In Handbook of Clinical Neurology. Vol. 142. Elsevier B.V. 2017. p. 57-70. (Handbook of Clinical Neurology). https://doi.org/10.1016/B978-0-444-63625-6.00006-9
Medici, Valentina ; Huster, Dominik. / Animal models of Wilson disease. Handbook of Clinical Neurology. Vol. 142 Elsevier B.V., 2017. pp. 57-70 (Handbook of Clinical Neurology).
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