Esrrb-flox Mouse

Esrrb, an estrogen-related receptor, is a member of the orphan nuclear receptor family. It mediates stem cell self-renewal, early embryonic development, and plays a role in regulating energy metabolism in mammals. It is also involved in crucial biological processes such as pluripotency, cell-cycle regulation, and differentiation. Genetic models, especially KO mouse models, are valuable for studying its functions [2].

Knocking out Esrrb in cervical cancer cells using CRISPR/Cas9 led to cell-cycle arrest at the G0-G1 to S phase transition, inhibiting cell proliferation in vitro and tumor growth in vivo, indicating its tumor-promoting function in cervical cancer by inhibiting the TGFβ signaling pathway [1]. In murine embryonic stem cell models, genetic inactivation of Esrrb caused illegitimate expression of mesendoderm and extra-embryonic markers, impaired formative expression, and failure to self-organize in 3D, highlighting its role in guiding naive pluripotent cells through the formative transcriptional programme [3]. Esrrb-null embryos and enhancer knockout embryos had reduced Bmp4 expression in the extra-embryonic ectoderm and fewer primordial germ cells, suggesting Esrrb functions as an upstream factor of Bmp4 in regulating proper primordial germ cell development [4].

In conclusion, Esrrb is essential for stem cell self-renewal, early embryonic development, and pluripotency. Through KO mouse models, its role in diseases like cervical cancer has been revealed, where it promotes tumor growth. In embryonic development, it is crucial for processes such as primordial germ cell development and the transition of naive pluripotent cells, contributing to our understanding of these biological processes and potentially relevant disease mechanisms.