Ctnnb1, which codes for β-catenin, is a key regulatory molecule of the Wnt/β-catenin signaling pathway [2]. This pathway is pivotal in organ development, tissue homeostasis, cell proliferation, differentiation, and function [2]. Genetic models, such as knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying Ctnnb1's functions.

In intestinal epithelia, knockout of an upstream enhancer of Ctnnb1 named ieCtnnb1 led to reduced Ctnnb1 transcription, compromising the canonical Wnt signaling in intestinal crypts [1]. Single-cell sequencing showed that this knockout altered epithelial compositions and potentially compromised functions of small intestinal crypts [1]. While it hampered epithelial turnovers in normal conditions, it prevented the occurrence and progression of Wnt/β-catenin-driven colorectal cancers [1].

In conclusion, Ctnnb1 is essential for maintaining tissue homeostasis through the Wnt/β-catenin signaling pathway. The study of Ctnnb1 KO models, like the ieCtnnb1 knockout, has provided insights into its role in intestinal homeostasis and colorectal cancer development, highlighting its significance in understanding these biological processes and disease conditions.

References:

1. Hua, Xiaojiao, Zhao, Chen, Tian, Jianbo, Liu, Ying, Zhou, Yan. 2024. A Ctnnb1 enhancer transcriptionally regulates Wnt signaling dosage to balance homeostasis and tumorigenesis of intestinal epithelia. In eLife, 13, . doi:10.7554/eLife.98238. https://pubmed.ncbi.nlm.nih.gov/39320349/

2. Agaimy, Abbas, Haller, Florian. . CTNNB1 (β-Catenin)-altered Neoplasia: A Review Focusing on Soft Tissue Neoplasms and Parenchymal Lesions of Uncertain Histogenesis. In Advances in anatomic pathology, 23, 1-12. doi:10.1097/PAP.0000000000000104. https://pubmed.ncbi.nlm.nih.gov/26645457/