Aragao-Santiago Leticia, Gomez-Sanchez Celso E, Mulatero Paolo, Spyroglou Ariadni, Reincke Martin, Williams Tracy Ann
Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Germany.
Endocrinology Division, G.V. (Sonny) Montgomery Veterans Affairs Medical Center and University of Mississippi Medical Center.
Endocrinology. 2017 Dec 1;158(12):4129-4138. doi: 10.1210/en.2017-00637.
Primary aldosteronism (PA) is a common form of endocrine hypertension that is characterized by the excessive production of aldosterone relative to suppressed plasma renin levels. PA is usually caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations have been identified in several genes that encode ion pumps and channels that may explain the aldosterone excess in over half of aldosterone-producing adenomas, whereas the pathophysiology of bilateral adrenal hyperplasia is largely unknown. A number of mouse models of hyperaldosteronism have been described that recreate some features of the human disorder, although none replicate the genetic basis of human PA. Animal models that reproduce the genotype-phenotype associations of human PA are required to establish the functional mechanisms that underlie the endocrine autonomy and deregulated cell growth of the affected adrenal and for preclinical studies of novel therapeutics. Herein, we discuss the differences in adrenal physiology across species and describe the genetically modified mouse models of PA that have been developed to date.
原发性醛固酮增多症（PA）是一种常见的内分泌性高血压，其特征是醛固酮分泌过多而血浆肾素水平受到抑制。PA通常由单侧醛固酮分泌腺瘤或双侧肾上腺增生引起。在几个编码离子泵和通道的基因中已发现体细胞突变，这可能解释了超过一半的醛固酮分泌腺瘤中醛固酮过多的原因，而双侧肾上腺增生的病理生理学在很大程度上尚不清楚。已经描述了许多醛固酮增多症的小鼠模型，这些模型重现了人类疾病的一些特征，尽管没有一个模型能复制人类PA的遗传基础。需要能够重现人类PA基因型-表型关联的动物模型来确定受影响肾上腺内分泌自主性和细胞生长失调的功能机制，并用于新型疗法的临床前研究。在此，我们讨论了不同物种肾上腺生理学的差异，并描述了迄今为止已开发的PA基因工程小鼠模型。
