| First Author | Mittal P | Year | 2015 |
| Journal | J Clin Invest | Volume | 125 |
| Issue | 8 | Pages | 3280-4 |
| PubMed ID | 26193636 | Mgi Jnum | J:222990 |
| Mgi Id | MGI:5646199 | Doi | 10.1172/JCI81534 |
| Citation | Mittal P, et al. (2015) Med12 gain-of-function mutation causes leiomyomas and genomic instability. J Clin Invest 125(8):3280-4 |
| abstractText | Uterine leiomyomas are benign tumors that can cause pain, bleeding, and infertility in some women. Mediator complex subunit 12 (MED12) exon 2 variants are associated with uterine leiomyomas; however, the causality of MED12 variants, their genetic mode of action, and their role in genomic instability have not been established. Here, we generated a mouse model that conditionally expresses a Med12 missense variant (c.131G>A) in the uterus and demonstrated that this alteration alone promotes uterine leiomyoma formation and hyperplasia in both WT mice and animals harboring a uterine mesenchymal cell-specific Med12 deletion. Compared with WT animals, expression of Med12 c.131G>A in conditional Med12-KO mice resulted in earlier onset of leiomyoma lesions that were also greater in size. Moreover, leiomyomatous, Med12 c.131G>A variant-expressing uteri developed chromosomal rearrangements. Together, our results show that the common human leiomyoma-associated MED12 variant can cause leiomyomas in mice via a gain of function that drives genomic instability, which is frequently observed in human leiomyomas. |
