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Relevance of animal models for understanding mammalian copper homeostasis^1,2,3,4

¹ From the Department of Metabolic and Endocrine Disease (WIMV and BvdS) and the Complex Genetics Section, DBG-Department of Medical Genetics (WIMV, CW, and BvdS), University Medical Center Utrecht, Utrecht, Netherlands, and the Department of Genetics (CW) and the Department of Pathology and Laboratory Medicine (BvdS), University Medical Center Groningen, University of Groningen, Groningen, Netherlands

ABSTRACT

As a trace element, copper has a crucial role in mammalian metabolism, but it can be toxic in excess. The importance of a balanced copper homeostasis is illustrated by several copper-associated disorders in man, such as Menkes and Wilson disease, and in a wide variety of animal models (eg, mice, dogs, and sheep). Proteins involved in controlling copper metabolism have been well studied in yeast and in vitro. Recently, naturally occurring mutants and transgenic mouse models have been used to study the physiologic role of copper transporters in copper homeostasis. We discuss the most common mammalian animal models used to study copper-related diseases, evaluate what these model systems have recently shown about copper metabolism, and discuss the importance of these models for identifying specific and sensitive biomarkers associated with copper status in the near future.

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