The Pathogenesis of Haemochromatosis in the HFE Knockout Mouse Model

遗传性血色素沉着症是一种非常常见的遗传性疾病，大约每200名澳大利亚人中就有一人患病。它改变了身体利用铁的方式。它会增加膳食中铁的吸收，并增加铁在人体主要器官如肝脏、心脏和胰腺中的沉积。这种铁对身体组织有害，可能会导致肝硬变、心脏病、糖尿病和恶性肿瘤。遗传性血色病患者中存在缺陷的基因已被鉴定为HFE，然而，HFE的功能尚不清楚。最近，一种很好的这种疾病的实验室模型已经被开发出来。我们的目标是利用这个模型首次展示HFE如何控制身体吸收的铁量，以及有多少铁被输送到肝脏等组织。我们还旨在确定遗传性血色素沉着症患者的这些过程是如何受损的。通过这项研究，我们将更好地了解HFe在正常和遗传性血色素沉着症患者铁代谢中的作用，这将为开发预防或治疗铁超载的新疗法提供机会。

Hereditary haemochromatosis is a very common genetic disease that affects approximately 1 in 200 Australians. It alters the way the body uses iron. It causes an increase in absorption of dietary iron and increased deposition of iron in major organs of the body such as the liver, heart and pancreas. This iron is harmful to tissues in the body and may lead to the development of liver cirrhosis, heart disease, diabetes and malignancy. The gene that is defective in hereditary haemochromatosis patients has been identified and called HFE however, the function of HFE is not known. Recently, an excellent laboratory model of this disease has been developed. We aim to use this model to show for the first time how HFE controls the amount of iron the body absorbs and how much iron is delivered to tissues such as the liver. We also aim to identify how these processes are impaired in hereditary haemochromatosis patients. From this study, we will gain a better understanding of the role of HFE in iron metabolism of normal and hereditary haemochromatosis patients and this will provide opportunities for the development of new therapies for the prevention or treatment of iron overload.