Lyz1-KO Mouse

Lyz1, encoding C-type lysozyme, is a β-1,4-N-acetylmuramoylhydrolase produced mainly by Paneth cells. It enzymatically processes bacterial cell walls, playing a crucial role in the innate immune response and influencing the composition of gut microbiota. It may also be involved in signaling pathways related to inflammation [1,2,3,4,5]. Genetic models, such as gene knockout mice, have been instrumental in studying its functions.

Targeted disruption of Lyz1 in mice protected them from experimental colitis, diminished intestinal immune responses to bacterial molecular patterns, and led to the expansion of lysozyme-sensitive mucolytic bacteria like Ruminococcus gnavus [1]. Lyz1 -/- mice were also protected from Salmonella Typhimurium-induced infection in terms of morbidity, mortality, and barrier integrity, while ectopic Lyz1-expressing mice had exacerbated infection and inflammation as lysozyme-Salmonella encounter released barrier-disrupting factors [3]. Atf4ΔIEC mice with decreased Lyz1 expression due to ATF4 deficiency developed more severe colitis, and Lyz1 deficiency in mice reduced circulating Nod2 ligand, IgG production, and T-cell-specific cytokines after oral immunization [4,5].

In conclusion, Lyz1 is essential for maintaining the balance between anti-and pro-inflammatory responses in the intestine. Gene knockout mouse models have revealed its role in colitis, response to bacterial infections, and immune regulation, providing insights into inflammatory bowel diseases and related conditions [1,3,4,5].

References:

1. Yu, Shiyan, Balasubramanian, Iyshwarya, Laubitz, Daniel, Kiela, Pawel R, Gao, Nan. . Paneth Cell-Derived Lysozyme Defines the Composition of Mucolytic Microbiota and the Inflammatory Tone of the Intestine. In Immunity, 53, 398-416.e8. doi:10.1016/j.immuni.2020.07.010. https://pubmed.ncbi.nlm.nih.gov/32814028/

2. Su, Xiaomin, Jin, Mengli, Xu, Chen, Zhang, Yuan, Yang, Rongcun. . FABP4 in Paneth cells regulates antimicrobial protein expression to reprogram gut microbiota. In Gut microbes, 14, 2139978. doi:10.1080/19490976.2022.2139978. https://pubmed.ncbi.nlm.nih.gov/36519446/

3. Han, Jiangmeng, Balasubramanian, Iyshwarya, Flores, Juan A, Ferraris, Ronaldo, Gao, Nan. 2024. Intestinal lysozyme engagement of Salmonella Typhimurium stimulates the release of barrier-impairing InvE and Lpp1. In The Journal of biological chemistry, 300, 107424. doi:10.1016/j.jbc.2024.107424. https://pubmed.ncbi.nlm.nih.gov/38823640/

4. Hu, Xiaoming, Deng, Jiali, Yu, Tianming, Liu, Zhanju, Guo, Feifan. 2018. ATF4 Deficiency Promotes Intestinal Inflammation in Mice by Reducing Uptake of Glutamine and Expression of Antimicrobial Peptides. In Gastroenterology, 156, 1098-1111. doi:10.1053/j.gastro.2018.11.033. https://pubmed.ncbi.nlm.nih.gov/30452920/

5. Wang, Haifang, Shen, Xueying, Zheng, Xiaojiao, Zhang, Qin, Liu, Zhihua. 2021. Intestinal lysozyme releases Nod2 ligand(s) to promote the intestinal mucosal adjuvant activity of cholera toxin. In Science China. Life sciences, 64, 1720-1731. doi:10.1007/s11427-020-1862-8. https://pubmed.ncbi.nlm.nih.gov/33521852/