Muc2-KO Mouse

MUC2, a subtype of secretory mucins, is produced by goblet cells and is the major macromolecular component of mucus in the gut mucosa [2]. Its primary function is to form a protective mucus barrier between epithelial surfaces and the gut lumen, preventing direct contact between intestinal bacteria and colonic epithelial cells, thus playing a crucial role in gut barrier function and homeostasis [1,2,4,5]. The production of MUC2 is regulated by various bioactive molecules, signaling pathways, and gut microbiota, forming a complex regulatory network [2].

In ulcerative colitis (UC), bacterial factors related to the MUC2 mucus barrier are involved in dietary pattern response, MUC2 mucus barrier dysfunction, contact stimulation with colonic epithelial cells, and mucosal and submucosal inflammation [1]. In colorectal cancer (CRC), MUC2 disruption is associated with the disease, and its expression is regulated by various modulators, being related to immunomodulation, tumor immunity, and microbiota regulation [3]. In breast cancer, MUC2 affects cancer cell proliferation, response to chemotherapy, and metastasis [7]. Also, in pancreatic neoplasia, MUC2 is rarely detectable in aggressive tumors but commonly expressed in indolent ones, suggesting potential diagnostic and prognostic value [6]. Additionally, MUC2 gene methylation detection in feces and blood shows promise as a new screening and early-diagnosis method for pancreatic cancer [8].

In summary, MUC2 is essential for maintaining gut barrier function and homeostasis. Its dysregulation is associated with multiple diseases, including UC, CRC, breast cancer, pancreatic neoplasia, and pancreatic cancer. Research on MUC2 using genetic models helps in understanding the underlying mechanisms of these diseases, potentially leading to new therapeutic strategies.

References:

1. Yao, Dianbo, Dai, Wanlin, Dong, Ming, Dai, Chaoliu, Wu, Shuodong. 2021. MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis. In EBioMedicine, 74, 103751. doi:10.1016/j.ebiom.2021.103751. https://pubmed.ncbi.nlm.nih.gov/34902790/

2. Liu, Yaxin, Yu, Zihan, Zhu, Lanping, Guli, Sitan, Chen, Xin. 2023. Orchestration of MUC2 - The key regulatory target of gut barrier and homeostasis: A review. In International journal of biological macromolecules, 236, 123862. doi:10.1016/j.ijbiomac.2023.123862. https://pubmed.ncbi.nlm.nih.gov/36870625/

3. Gundamaraju, Rohit, Chong, Wai Chin. 2021. Consequence of distinctive expression of MUC2 in colorectal cancers: How much is actually bad? In Biochimica et biophysica acta. Reviews on cancer, 1876, 188579. doi:10.1016/j.bbcan.2021.188579. https://pubmed.ncbi.nlm.nih.gov/34139275/

4. Allen, A, Hutton, D A, Pearson, J P. . The MUC2 gene product: a human intestinal mucin. In The international journal of biochemistry & cell biology, 30, 797-801. doi:. https://pubmed.ncbi.nlm.nih.gov/9722984/

5. Liu, Yang, Yu, Xinjie, Zhao, Jianxin, Zhai, Qixiao, Chen, Wei. 2020. The role of MUC2 mucin in intestinal homeostasis and the impact of dietary components on MUC2 expression. In International journal of biological macromolecules, 164, 884-891. doi:10.1016/j.ijbiomac.2020.07.191. https://pubmed.ncbi.nlm.nih.gov/32707285/

6. Levi, E, Klimstra, D S, Andea, A, Basturk, O, Adsay, N V. . MUC1 and MUC2 in pancreatic neoplasia. In Journal of clinical pathology, 57, 456-62. doi:. https://pubmed.ncbi.nlm.nih.gov/15113850/

7. Astashchanka, Anna, Shroka, Thomas M, Jacobsen, Britta M. 2018. Mucin 2 (MUC2) modulates the aggressiveness of breast cancer. In Breast cancer research and treatment, 173, 289-299. doi:10.1007/s10549-018-4989-2. https://pubmed.ncbi.nlm.nih.gov/30317423/

8. Zhou, Hanyu, Zhu, Yingwei, Wei, Feifei, Xu, Kequn, Cheng, Yuqing. 2019. Significance of MUC2 gene methylation detection in pancreatic cancer diagnosis. In Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 19, 1049-1053. doi:10.1016/j.pan.2019.09.012. https://pubmed.ncbi.nlm.nih.gov/31590960/