Meg3 Knockout in β Cells and Pituitary

Vaishali I Parekh, Hui Sun, Min Chen, Lee S Weinstein, Sunita K Agarwal
Journal of the Endocrine Society, Volume 6, Issue 11, November 2022, bvac141
https://doi.org/10.1210/jendso/bvac141

Abstract

Context

Maternally expressed gene 3 (MEG3) is a long noncoding RNA (lncRNA) that has been implicated as a tumor suppressor.

Objective

The expression of MEG3 RNA is downregulated in various human tumors, including pituitary adenoma and pancreatic islet tumors due to MEG3 gene deletion or DNA hypermethylation. Mouse models with conventional germline deletion of Meg3 have shown that Meg3 is essential for perinatal or postnatal development and survival. However, a direct role of Meg3 loss in tumorigenesis has not been shown.

Methods

To observe a causal relationship between Meg3 loss and tumorigenesis, we have generated a mouse model with conditional deletion of Meg3 mediated by the RIP-Cre transgene that initiated Meg3 deletion in pancreatic islet β cells and anterior pituitary.

Results

Meg3 loss did not lead to the development of islet tumors. Interestingly, RIP-Cre–mediated Meg3 loss led to the development of an enlarged pituitary. The genes in the Meg3 region are transcribed together as a 210 kb RNA that is processed into Meg3 and other transcripts. Whether these tandem transcripts play a functional role in the growth of pancreatic endocrine cells and pituitary cells remains to be determined.

Conclusion

Our mouse model shows that Meg3 loss leads to hyperplasia in the pituitary and not in pancreatic islets, thus serving as a valuable model to study pathways associated with pituitary cell proliferation and function. Future mouse models with specific inactivation of Meg3 alone or other transcripts in the Meg3 polycistron are warranted to study tissue-specific effects on initiating neoplasia and tumor development.

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