Related Experiment Videos
Heterozygous Men1 mutant mice develop a range of endocrine tumors mimicking multiple endocrine neoplasia type 1
Philippe Bertolino1, Wei-Min Tong, Dominique Galendo
1Laboratory of Genetics, Centre National de la Recherche Scientifique, Faculty of Medicine, University of Lyon, Lyon, France.
Abstract:
Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome characterized by the occurrence of multiple endocrine tumors of the parathyroid, pancreas, and anterior pituitary in patients. To study tumorigenesis related to the MEN1 syndrome, we have generated Men1 knockout mice using the gene targeting approach. Heterozygous Men1 mutant mice developed the same range of major endocrine tumors as is seen in MEN1 patients, affecting the parathyroid, pancreatic islets, pituitary and adrenal glands, as well as the thyroid, and exhibiting multistage tumor progression with metastatic potential. In particular, extrapancreatic gastrinoma, pancreatic glucagonoma, and mixed hormone-producing tumors in islets were observed. In addition, there was a high incidence of gonadal tumors of endocrine origin, i.e. Leydig cell tumors, and ovary sex-cord stromal cell tumors in heterozygous Men1 mutant mice. Hormonal disturbance, such as abnormal PTH and insulin levels, was also observed in these mice. These tumors were associated with loss of heterozygosity of the wild-type Men1 allele, suggesting that menin is involved in suppressing the development of these endocrine tumors. All of these features are reminiscent of MEN1 symptoms in humans and establish heterozygous Men1 mutant mice as a suitable model for this disease.
Insights
Researchers created Men1 knockout mice to study multiple endocrine neoplasia type 1 (MEN1). These mice developed tumors in endocrine glands, mirroring human MEN1 symptoms and providing a valuable disease model.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Multiple endocrine neoplasia type 1 (MEN1) is an inherited disorder causing tumors in endocrine glands.
- Understanding MEN1 tumorigenesis is crucial for developing effective treatments.
Purpose of the Study:
- To establish a mouse model for studying MEN1 syndrome.
- To investigate the role of the Men1 gene in endocrine tumor development.
Main Methods:
- Gene targeting was used to create Men1 knockout mice.
- Tumor development, hormonal levels, and genetic alterations were analyzed in heterozygous Men1 mutant mice.
Main Results:
- Heterozygous Men1 mutant mice developed a spectrum of endocrine tumors, including parathyroid, pancreatic, pituitary, adrenal, and thyroid tumors.
- Tumors exhibited multistage progression, metastatic potential, and included rare types like extrapancreatic gastrinoma and glucagonoma.
- A high incidence of gonadal endocrine tumors (Leydig cell and sex-cord stromal cell tumors) was observed.
- Loss of heterozygosity of the wild-type Men1 allele was associated with tumor development.
Conclusions:
- Heterozygous Men1 mutant mice accurately recapitulate key features of human MEN1.
- This mouse model is suitable for studying MEN1 pathogenesis and evaluating therapeutic strategies.