Sumo1-KO Mouse

SUMO1, short for Small Ubiquitin-related Modifier 1, is involved in a dynamic post-translational modification process called SUMOylation. This modification plays a crucial role in maintaining cardiac function, protecting against hypertrophic responses to cardiac pressure overload, and is also associated with nearly every aspect of cellular function [1,2]. SUMOylation pathways are important for embryonic development as global inhibition of SUMO conjugation in mice leads to embryonic lethality [4].

In myocardial infarction (MI) studies, SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury. Single-nucleus RNA sequencing revealed differential roles of SUMO1 in regulating heart cells. For example, in cardiomyocytes, SUMO1 deletion increased the Nppa + Nppb + Ankrd1 + cardiomyocyte subcluster proportion after MI. In fibroblasts, the conversion to myofibroblasts subclusters was inhibited in SUMO1 knockout mice, while in endothelial cells, SUMO1 loss promoted the proliferation of subsets capable of re-establishing neovascularization [1]. In experimental sepsis, global genetic depletion of SUMO1 enhanced TNFα production and metabolic acidosis, suggesting that splenic SUMO1 can modulate immune and metabolic responses to bacterial infection [3].

In conclusion, SUMO1 is essential for maintaining normal cellular and physiological functions. Model-based research, especially SUMO1 knockout mouse models, has revealed its significant roles in cardiac repair after MI and in modulating immune and metabolic responses during sepsis. These findings provide new insights into the pathogenesis of related diseases and potential therapeutic targets.

References:

1. Liu, Zhihao, Liu, Xiaozhi, Liu, Li, Bian, Xiyun, Fan, Guanwei. 2022. SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity. In Journal of pharmaceutical analysis, 13, 170-186. doi:10.1016/j.jpha.2022.11.010. https://pubmed.ncbi.nlm.nih.gov/36908856/

2. Wang, Wei, Matunis, Michael J. 2023. Paralogue-Specific Roles of SUMO1 and SUMO2/3 in Protein Quality Control and Associated Diseases. In Cells, 13, . doi:10.3390/cells13010008. https://pubmed.ncbi.nlm.nih.gov/38201212/

3. Youssef, Ayman, Mohammed, Bilal Khan, Prasad, Abhishek, Yang, Wei, Ulloa, Luis. 2023. Splenic SUMO1 controls systemic inflammation in experimental sepsis. In Frontiers in immunology, 14, 1200939. doi:10.3389/fimmu.2023.1200939. https://pubmed.ncbi.nlm.nih.gov/37520526/

4. Lee, Andreia, Zhu, Yiping, Sabo, Yosef, Goff, Stephen P. 2019. Embryonic Cells Redistribute SUMO1 upon Forced SUMO1 Overexpression. In mBio, 10, . doi:10.1128/mBio.01856-19. https://pubmed.ncbi.nlm.nih.gov/31796536/