Lancl1-KO Mouse

Lancl1, or Lanthionine synthetase C-like protein 1, is an antioxidant-related protein. It is involved in multiple biological pathways such as those related to oxidative stress regulation. It binds to abscisic acid (ABA) and activates the AMPK/PGC-1α/Sirt1 pathway, influencing glucose transport, mitochondrial respiration, and energy metabolism [3]. Lancl1 is also crucial for maintaining redox homeostasis in various cell types, highlighting its overall biological importance. Genetic models, like gene-knockout (KO) mouse models, are valuable for studying its functions.

In KO mouse models, Lancl1-deficient mice display spermatozoal oxidative damage and impaired male fertility, indicating its role in testicular homeostasis and male fertility regulated by redox balance [4]. In ALS transgenic SOD1G93A mouse models, CNS-specific deletion of Lancl1 leads to neurodegenerative phenotypes, while its overexpression extends lifespan, delays disease onset, and improves motor performance, suggesting it is a positive regulator of AKT activity and a potential therapeutic target in ALS [2]. Prolonged isoflurane anesthesia in animal models reduces Lancl1 expression, causing neurotoxicity, and overexpression of Lancl1 can mitigate this neurotoxic effect, protecting developing neurons [1].

In conclusion, Lancl1 plays essential roles in maintaining redox homeostasis in different biological systems. Model-based research, especially KO/CKO mouse models, has revealed its significance in diseases such as male subfertility, ALS, and anesthesia-induced neurotoxicity. Understanding Lancl1 functions provides potential therapeutic strategies for these conditions.

References:

1. Xie, Wenjia, Xi, Yuqing, Dong, Daoqian, Xia, Tianjiao, Gu, Xiaoping. 2024. LanCL1 protects developing neurons from long-term isoflurane anesthesia-induced neurotoxicity. In Experimental neurology, 381, 114880. doi:10.1016/j.expneurol.2024.114880. https://pubmed.ncbi.nlm.nih.gov/38972370/

2. Tan, Honglin, Chen, Mina, Pang, Dejiang, Worley, Paul F, Xiao, Bo. 2019. LanCL1 promotes motor neuron survival and extends the lifespan of amyotrophic lateral sclerosis mice. In Cell death and differentiation, 27, 1369-1382. doi:10.1038/s41418-019-0422-6. https://pubmed.ncbi.nlm.nih.gov/31570855/

3. Spinelli, Sonia, Begani, Giulia, Guida, Lucrezia, Zocchi, Elena, Sturla, Laura. 2021. LANCL1 binds abscisic acid and stimulates glucose transport and mitochondrial respiration in muscle cells via the AMPK/PGC-1α/Sirt1 pathway. In Molecular metabolism, 53, 101263. doi:10.1016/j.molmet.2021.101263. https://pubmed.ncbi.nlm.nih.gov/34098144/

4. Huang, Chao, Yang, Chengcheng, Pang, Dejiang, Xiao, Bo, Chen, Zhengli. 2022. Animal models of male subfertility targeted on LanCL1-regulated spermatogenic redox homeostasis. In Lab animal, 51, 133-145. doi:10.1038/s41684-022-00961-w. https://pubmed.ncbi.nlm.nih.gov/35469022/