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Neuroendocrinology

Mind the (human-based new approach methodology) gap!

Nature Reviews Endocrinology volume 20, page 509 (2024)Cite this article

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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.

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References

Original article

  • Mellon, P. L. et al. Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. Neuron 5, 1–10 (1990)

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Related article

  • Belsham, D. D. et al. Generation of a phenotypic array of hypothalamic neuronal cell models to study complex neuroendocrine disorders. Endocrinology 145, 393–400 (2004)

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Authors and Affiliations

  1. Department of Physiology, University of Toronto, Ontario, Canada

    Denise D. Belsham

  2. Department of Medicine, University of Toronto, Ontario, Canada

    Denise D. Belsham

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  1. Denise D. Belsham
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Correspondence to Denise D. Belsham.

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The author declares no competing interests.

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Belsham, D.D. Mind the (human-based new approach methodology) gap!. Nat Rev Endocrinol 20, 509 (2024). https://doi.org/10.1038/s41574-024-01011-w

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