Lyn-KO Mouse

Lyn, also known as Lck/yes-related protein tyrosine kinase, belongs to the Src family kinases (SFKs). It exerts numerous biological functions, including modulation in receptor-mediated intracellular signaling and intercellular communication. Lyn is involved in multiple pathways such as the IgE/FcεRI signaling pathway related to allergy, and it plays a key role in immunoreceptor signaling in myeloid immune cells and B lymphocytes [2,3].

Lyn -/- mice develop an SLE-like disease with plasma cell hyperplasia, indicating its crucial role in negative signaling within B cells [4]. In sepsis-associated acute kidney injury (SA-AKI), Lyn protected against renal tubular injury in the cecal ligation and puncture (CLP) induced AKI mouse model by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation and cell apoptosis. Pretreatment with Lyn agonist MLR-1023 also improved renal function [1]. Pharmacological inhibition or genetic depletion of Lyn, specifically, blocked the secretion of Dengue and Zika infectious particles and their corresponding virus-like particles (VLPs) [5].

In conclusion, Lyn is an essential regulator in various biological processes and disease conditions. Gene-knockout mouse models have been crucial in revealing its role in autoimmune diseases like systemic lupus erythematosus, SA-AKI, and viral egress. Understanding Lyn's functions may offer new therapeutic targets for these and other related diseases.

References:

1. Li, Nannan, Lin, Guoxin, Zhang, Hao, Liu, Jishi, Tang, Juan. 2023. Lyn attenuates sepsis-associated acute kidney injury by inhibition of phospho-STAT3 and apoptosis. In Biochemical pharmacology, 211, 115523. doi:10.1016/j.bcp.2023.115523. https://pubmed.ncbi.nlm.nih.gov/37003346/

2. Brian, Ben F, Freedman, Tanya S. . The Src-family Kinase Lyn in Immunoreceptor Signaling. In Endocrinology, 162, . doi:10.1210/endocr/bqab152. https://pubmed.ncbi.nlm.nih.gov/34320188/

3. Sun, Yizhao, Yang, Yanlei, Zhao, Yang, Zhang, Yanfen, Liu, Zhongcheng. 2021. The role of the tyrosine kinase Lyn in allergy and cancer. In Molecular immunology, 131, 121-126. doi:10.1016/j.molimm.2020.12.028. https://pubmed.ncbi.nlm.nih.gov/33419562/

4. Brodie, Erica J, Infantino, Simona, Low, Michael S Y, Tarlinton, David M. 2018. Lyn, Lupus, and (B) Lymphocytes, a Lesson on the Critical Balance of Kinase Signaling in Immunity. In Frontiers in immunology, 9, 401. doi:10.3389/fimmu.2018.00401. https://pubmed.ncbi.nlm.nih.gov/29545808/

5. Li, Ming Yuan, Naik, Trupti Shivaprasad, Siu, Lewis Yu Lam, Evans, Matthew J, Sanyal, Sumana. 2020. Lyn kinase regulates egress of flaviviruses in autophagosome-derived organelles. In Nature communications, 11, 5189. doi:10.1038/s41467-020-19028-w. https://pubmed.ncbi.nlm.nih.gov/33060596/