Upk3b, encoding an integral membrane protein of the tetraspanin superfamily, is specifically expressed in the mesothelia of body cavities (such as the epicardium, pericardium, pleura, and peritoneum) and the urothelium of the urinary tract in adult mice under homeostatic conditions [2]. It has been associated with extracellular matrix signaling in the mature epicardium [1]. The gene may also play a role in stabilizing and strengthening the urothelial cell layer of the bladder [3]. Genetic models like knock-in alleles in embryonic stem cells have been used to study its function [2].

A creERT2 knock-in allele of Upk3b was generated to analyze its function. Morphological, histological, and molecular analyses of Upk3b-deficient mice did not detect changes in the differentiation or integrity of the urothelium and the mesothelia covering internal organs, suggesting that Upk3b may be dispensable for the development and integrity of these tissues [2].

In conclusion, while Upk3b is expressed in specific epithelia and is associated with extracellular matrix signaling in the mature epicardium, studies using gene-knockout mouse models have shown that it may not be essential for the development and integrity of urothelium and mesothelium. This contributes to our understanding of the development and function of these specialized epithelia and may have implications for related diseases such as mesothelioma where Upk3b has been proposed as a diagnostic marker [3].

References:

1. Du, Jianlin, Yuan, Xin, Deng, Haijun, Li, Yingrui, She, Qiang. 2023. Single-cell and spatial heterogeneity landscapes of mature epicardial cells. In Journal of pharmaceutical analysis, 13, 894-907. doi:10.1016/j.jpha.2023.07.011. https://pubmed.ncbi.nlm.nih.gov/37719196/

2. Rudat, Carsten, Grieskamp, Thomas, Röhr, Christian, Schuster-Gossler, Karin, Kispert, Andreas. 2014. Upk3b is dispensable for development and integrity of urothelium and mesothelium. In PloS one, 9, e112112. doi:10.1371/journal.pone.0112112. https://pubmed.ncbi.nlm.nih.gov/25389758/

3. Lennartz, Maximilian, Atug, Dennis, Dwertmann Rico, Sebastian, Steurer, Stefan, Fraune, Christoph. 2022. Analysis of More than 16,000 Human Tumor and Normal Tissues Identifies Uroplakin 3B as a Useful Diagnostic Marker for Mesothelioma and Normal Mesothelial Cells. In Diagnostics (Basel, Switzerland), 12, . doi:10.3390/diagnostics12102516. https://pubmed.ncbi.nlm.nih.gov/36292206/