Men1, encoding a 610-amino acid protein menin, is a tumor suppressor gene [1]. Mutations in Men1 lead to multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder. Menin interacts with transcription factors and chromatin-modifying proteins in cell signaling pathways such as transforming growth factor β/bone morphogenetic protein, Wnt/β-catenin, and Hedgehog, facilitating the understanding of MEN1-associated tumor pathogenesis [3].

Mouse models of MEN1, with loss-of-function mutations in the Men1 gene, closely resemble the human disease in terms of tumor spectrum and hormonal changes [4]. These models have been exploited for therapy-response studies testing novel drugs against neuroendocrine tumors (NETs), providing promising leads for treating MEN1-related NENs [2,4]. They help understand the function of Menin in tumorigenesis, which is conserved from flies to mammals [4].

In conclusion, Men1 plays a crucial role in preventing the development of endocrine tumors as a tumor suppressor gene. The Men1-knockout mouse models have significantly contributed to the understanding of MEN1-associated tumor biology and the exploration of potential therapies for treating MEN1-related diseases, especially neuroendocrine neoplasms [2,4].

References:

1. Thakker, Rajesh V, Newey, Paul J, Walls, Gerard V, Tonelli, Francesco, Brandi, Maria Luisa. 2012. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). In The Journal of clinical endocrinology and metabolism, 97, 2990-3011. doi:10.1210/jc.2012-1230. https://pubmed.ncbi.nlm.nih.gov/22723327/

2. Grozinsky-Glasberg, Simona, Lines, Kate E, Avniel-Polak, Shani, Bountra, Chas, Thakker, Rajesh V. . Preclinical drug studies in MEN1-related neuroendocrine neoplasms (MEN1-NENs). In Endocrine-related cancer, 27, R345-R355. doi:10.1530/ERC-20-0127. https://pubmed.ncbi.nlm.nih.gov/32590358/

3. Brandi, Maria Luisa, Agarwal, Sunita K, Perrier, Nancy D, Valk, Gerlof D, Thakker, Rajesh V. . Multiple Endocrine Neoplasia Type 1: Latest Insights. In Endocrine reviews, 42, 133-170. doi:10.1210/endrev/bnaa031. https://pubmed.ncbi.nlm.nih.gov/33249439/

4. Mohr, Hermine, Pellegata, Natalia S. 2017. Animal models of MEN1. In Endocrine-related cancer, 24, T161-T177. doi:10.1530/ERC-17-0249. https://pubmed.ncbi.nlm.nih.gov/28743793/