The 1980s marked the beginning of the era of molecular biology; the sky was the limit for new technologies using complex genetic constructs to create mouse models for use in every field of science. In particular, the area of endocrinology had a range of novel transgenic mouse models that encompassed knockouts and knockins that enabled the link from a phenotype to specific genes and gene networks to be elucidated. During this time, the use of transgenic mice to create new cell models was also emerging. The creativity was impressive.

The study by Mellon et al. stands out for me as a key seminal study that changed the landscape of gonadotropin-releasing hormone (GnRH) research, and of reproductive biology as a whole. Pamela Mellon — fresh off a post-doctoral fellowship at Harvard University with Tom Maniatis (the scientist who literally wrote the book on molecular cloning, which was a staple in all laboratories at the time) and at that time a new faculty member at the Salk Institute — was exploring new technologies to target tumorigenesis in rodents. The idea was to clone the 5′ regulatory regions of specific genes (in this case, rat Gnrh1) to the potent oncogene SV40 T-antigen with the goal of promoting the development of tumours in specific cell types. As GnRH is highly expressed and localized to the hypothalamus, the transgenic animals developed tumours in the brain that could be excised and grown as cell cultures in a dish. The availability of these cell models revolutionized the study of GnRH neurons and created a level and type of information that was not possible until this time.

20 世纪 80 年代标志着分子生物学时代的开始；使用复杂的基因结构来创建用于各个科学领域的小鼠模型的新技术的天空是无限的。特别是，内分泌学领域拥有一系列新型转基因小鼠模型，其中包括基因敲除和基因敲入，从而能够阐明表型与特定基因和基因网络的联系。在此期间，利用转基因小鼠创建新的细胞模型也出现了。创意令人印象深刻。

梅隆等人的研究。对我来说，这是一项重要的开创性研究，它改变了促性腺激素释放激素 (GnRH) 以及整个生殖生物学研究的格局。帕梅拉·梅隆（Pamela Mellon）——刚从哈佛大学获得博士后奖学金，与汤姆·马尼蒂斯（Tom Maniatis）（这位科学家确实写了一本关于分子克隆的书，这本书是当时所有实验室的主要内容），当时是索尔克的新教员研究所 - 正在探索针对啮齿动物肿瘤发生的新技术。这个想法是将特定基因（在本例中为大鼠Gnrh1 ）的 5' 调控区克隆到强癌基因 SV40 T 抗原上，目的是促进特定细胞类型中肿瘤的发展。由于 GnRH 高度表达并定位于下丘脑，转基因动物在大脑中形成肿瘤，可以将其切除并在培养皿中作为细胞培养物生长。这些细胞模型的出现彻底改变了 GnRH 神经元的研究，并创造了迄今为止不可能的信息水平和类型。