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Updated: Mar 21, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Histopathological changes induced by selective inactivation of menin on the thyroid gland in RET÷PTC3 and E7
Oana Maria Căpraru1, Nicole Berger, Nicolas Gadot
1Department of Histology, University of Medicine and Pharmacy of Tirgu Mures, Romania; prorector_int@umftgm.ro.
Abstract:
Multiple Endocrine Neoplasia Type 1 (MEN1) does not involve the thyroid gland, but animal studies have shown that mice with inactivation of menin could develop thyroid pathologies. The objective was to evaluate if the selective inactivation of menin in murine thyroid glands expressing RET÷PTC3 and E7 oncogenes, might induce an increased index of proliferation and a more rapid development of thyroid hyperplasia and÷or tumors. The thyroid glands of 77 mice aged 4-18 months (31 expressing the E7 oncogene and 25 the RET÷PTC3 oncogene) were analyzed for histological changes and Ki67 proliferation index. Fifty-two mice had selective inactivation of menin in the thyroid gland (16 mice with RET÷PTC3 oncogene and 19 mice with E7 oncogene). As compared to wild type, mice with inactivation of menin presented an increased Ki67 proliferation index. Mice presenting the E7 oncogene showed larger thyroid glands with a pattern of diffuse hyperplasia. Mice expressing the RET÷PTC3 oncogene presented larger thyroid glands compared to the wild type mice but smaller compared to E7 mice. The lesions in the RET÷PTC3 group were "proliferative papillary cystic changes" (60%), "cribriform" (16%), "solid" (8%) and a combination of these patterns in the rest of the thyroid glands. The inactivation of menin in the thyroid gland of young mice does not seem to change the histological pattern, but it influences the proliferation of follicular cells. Further molecular studies especially in aged mice are needed to better understand the correlation between certain oncogenes and the inactive status of menin.
Insights
Inactivating menin in mouse thyroids with oncogenes increased cell proliferation. While not altering histology, menin inactivation influenced follicular cell growth, suggesting a role in thyroid tumor development.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Multiple Endocrine Neoplasia Type 1 (MEN1) typically spares the thyroid.
- Animal studies indicate menin inactivation may lead to thyroid pathologies.
- The role of menin in thyroid oncogenesis requires further investigation.
Purpose of the Study:
- To assess if selective menin inactivation in murine thyroid glands with RET/PTC3 or E7 oncogenes increases proliferation and accelerates hyperplasia/tumor development.
- To evaluate the impact of menin inactivation on thyroid gland histology and cell proliferation in the presence of specific oncogenes.
Main Methods:
- Analysis of thyroid glands from 77 mice (aged 4-18 months) with or without selective menin inactivation.
- Mice models included those expressing E7 oncogene (31) or RET/PTC3 oncogene (25).
- Histological examination and Ki67 proliferation index assessment were performed.
Main Results:
- Menin inactivation in mice led to an increased Ki67 proliferation index compared to wild-type.
- E7 oncogene expression resulted in larger thyroid glands with diffuse hyperplasia.
- RET/PTC3 oncogene expression caused larger thyroid glands than wild-type but smaller than E7, with various lesion patterns including proliferative papillary cystic changes.
Conclusions:
- Selective menin inactivation in young mice thyroids influences follicular cell proliferation but does not alter histological patterns.
- Further studies in aged mice are necessary to elucidate the correlation between oncogenes and menin status in thyroid development.
- Menin inactivation appears to play a role in modulating thyroid cell proliferation in the context of specific oncogenes.
