Characterisation of the mechanisms of gastrointestinal and hepatic iron transport in hereditary haemochromatosis

遗传性血色病是一种非常常见的遗传性疾病，影响约1：200澳大利亚人。它改变了身体使用铁的方式。铁对健康至关重要，但过多的铁对身体有毒，并对器官造成有害损害。在遗传性血色病中，身体从饮食中吸收过多的铁，并且大部分额外的铁进入肝脏，在那里可能导致肝硬化和肝癌。一些多余的铁也会进入心脏、胰腺和关节，分别导致心力衰竭、糖尿病和关节炎。有几种类型的血色病是由不同基因的突变引起的，这些基因在铁代谢的调节中很重要。在这项研究中，我们将调查两种类型的血色病引起的基因突变称为HFE和转铁蛋白受体2。这些基因的缺陷如何导致铁过载尚不清楚。我们将使用HFE和转铁蛋白受体2基因突变的实验室模型，首次确定这些蛋白质如何控制身体从饮食中吸收的铁量以及将多少铁输送到肝脏等组织。通过这项研究，我们将更好地了解HFE和转铁蛋白受体2在正常铁代谢和血色病中的作用。这些新知识将为开发新的更有效的治疗方法来预防和治疗铁过载提供机会。

Hereditary haemochromatosis is a very common genetic disease that affects approximately 1:200 Australians. It alters the way the body uses iron. Iron is essential for health but too much iron is toxic to the body and causes harmful damage to organs. In hereditary haemochromatosis the body absorbs too much iron from the diet and most of the extra iron goes to the liver where it may cause liver cirrhosis and liver cancer. Some of the excess iron also goes to the heart, pancreas and joints where it can lead to heart failure, diabetes and arthritis, respectively. There are several types of haemochromatosis that are caused by mutations in different genes that are important in the regulation of iron metabolism. In this study we will investigate two types of haemochromatosis caused by mutations in genes called HFE and transferrin receptor 2. How defects in these genes cause iron overload is not known. We will use laboratory models that have mutations in HFE and transferrin receptor 2 genes to identify for the first time how these proteins control the amount of iron the body absorbs from the diet and how much iron to delivered to the tissues such as the liver. From this study, we will gain a better understanding of the role of HFE and transferrin receptor 2 in both normal iron metabolism and haemochromatosis. This new knowledge will provide opportunities for the development of new more effective therapies for the prevention and treatment of iron overload.