Lines K E, Stevenson M, Thakker R V
Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford OX3 7LJ, UK.
Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford OX3 7LJ, UK.
Mol Cell Endocrinol. 2016 Feb 5;421:68-81. doi: 10.1016/j.mce.2015.08.024. Epub 2015 Aug 28.
Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼ 30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies.
垂体肿瘤可作为复杂遗传性疾病的一部分出现,或更常见地作为散发性(非家族性)疾病出现。对导致此类垂体肿瘤的分子和遗传机制的研究已确定超过35个基因失调,其中许多是通过对小鼠、大鼠和斑马鱼的研究发现的。用于生成这些动物模型的策略包括基因敲除、基因敲入和转基因过表达,以及化学诱变和药物诱导。这些动物模型为研究组织特异性肿瘤发生机制和评估新疗法提供了重要资源,对多发性内分泌腺瘤1型(MEN1)的研究就说明了这一点,MEN1是一种遗传性综合征,约30%的患者会发生垂体腺瘤。本文综述了已建立的垂体肿瘤动物模型,以及基因编辑技术的一些最新进展,并举例说明了使用Men1小鼠作为评估新疗法的临床前模型。