Background: Wnt/beta-catenin signaling plays a regulatory role in uterine development and function. To study this role of Wnt/beta-catenin signaling during embryogenesis in more detail, we employed an AmhR2 promoter-driven C-recombinase (Jamin et al., 2002) to conditionally inactivate the Apc gene in mesenchymal cells surrounding the müllerian duct. As a consequence of Apc inactivation, defects in the destruction complex are expected to result in the intracellular accumulation of beta-catenin and the subsequent constitutive activation of canonical Wnt signaling.

Methods: [Apc15Lox/15lox;AmhR2-Cre] conditional Apc knockout mice were generated. Cre expression and AmhR2 promotor activity was verified by staining for beta-galactosidase activity in [AmhR2-LacZ] and [AmhR2-Cre;ROSA26-LacZlox] reporter mice. Furthermore, recombination of the Apc gene was verified for different laser micro-dissected regions of the uterus, from 8-week-old mice, by PCR. Uterine defects were examined by immunohistochemical staining for various uterine markers.

Results: It was observed that the Cre-mediated Apc gene deletion mainly took place in the myometrial layers of the uterus. Recombination in the stroma and epithelium of the lumen and glands was low. Microscopically, the affected mice showed a significant reduction in the number of glands and a somewhat disorganized stroma. The main defects, however, were observed in the myometrial layer of the uterus, where clear disorganization of muscle fibres and in 50% of cases visible loss of musculature was apparent. As a consequence of these defects, the mice displayed reduced litter sizes and some mice were incapable of normal delivery.

Conclusion: AmhR2-Cre driven embryonic knock-down of Apc results in a defect of the myometrial layer of the uterus. Effects on the endometrium were observed to be less profound.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4208.