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Animal models of MEN1
Hermine Mohr1, Natalia S Pellegata2
1Institute for Diabetes and CancerHelmholtz Zentrum München, Neuherberg, Germany.
Abstract:
Animal models of cancer have been instrumental in advancing our understanding of the biology of tumor initiation and progression, in studying gene function and in performing preclinical studies aimed at testing novel therapies. Several animal models of the MEN1 syndrome have been generated in different organisms by introducing loss-of-function mutations in the orthologues of the human MEN1 gene. In this review, we will discuss MEN1 and MEN1-like models in Drosophila, mice and rats. These model systems with their specific advantages and limitations have contributed to elucidate the function of Menin in tumorigenesis, which turned out to be remarkably conserved from flies to mammals, as well as the biology of the disease. Mouse models of MEN1 closely resemble the human disease in terms of tumor spectrum and associated hormonal changes, although individual tumor frequencies are variable. Rats affected by the MENX (MEN1-like) syndrome share some features with MEN1 patients albeit they bear a germline mutation in Cdkn1b (p27) and not in Men1 Both Men1-knockout mice and MENX rats have been exploited for therapy-response studies testing novel drugs for efficacy against neuroendocrine tumors (NETs) and have provided promising leads for novel therapies. In addition to presenting well-established models of MEN1, we also discuss potential models which, if implemented, might broaden even further our knowledge of neuroendocrine tumorigenesis. In the future, patient-derived xenografts in zebrafish or mice might allow us to expand the tool-box currently available for preclinical studies of MEN1-associated tumors.
Insights
Animal models, including Drosophila, mice, and rats, are crucial for studying the multiple endocrine neoplasia type 1 (MEN1) syndrome. These models help elucidate Menin
Area of Science:
- Oncology
- Endocrinology
- Genetics
Background:
- Animal models are vital for understanding cancer biology, gene function, and preclinical therapy testing.
- The multiple endocrine neoplasia type 1 (MEN1) syndrome is studied using various animal models with mutations in the human MEN1 gene orthologues.
Purpose of the Study:
- To review existing and potential animal models for MEN1 and MEN1-like syndromes.
- To discuss the contribution of these models to understanding Menin function in tumorigenesis and disease biology.
- To highlight the utility of models in preclinical therapy response studies for neuroendocrine tumors (NETs).
Main Methods:
- Review of established and emerging animal models for MEN1 syndrome.
- Analysis of genetic mutations (e.g., Men1, Cdkn1b) in Drosophila, mice, and rats.
- Discussion of preclinical therapy response studies using MEN1 models.
Main Results:
- Menin's function in tumorigenesis is conserved across species from flies to mammals.
- Mouse models closely mimic human MEN1 tumors and hormonal changes, though frequencies vary.
- MENX rats (Cdkn1b mutation) exhibit MEN1-like features and are used for NET therapy testing.
Conclusions:
- Animal models, including mice and rats, are indispensable tools for MEN1 research.
- These models have significantly advanced the understanding of MEN1 biology and identified potential therapies for NETs.
- Future models like patient-derived xenografts may further enhance preclinical studies for MEN1-associated tumors.
