Fbxl22-KO Mouse

Fbxl22, or F-box and leucine-rich protein 22, is an E3 ubiquitin ligase. It is involved in the ubiquitin-proteasome system, regulating protein degradation. In muscle, it has a role in muscle homeostasis and atrophy processes, and in the heart, it is crucial for maintaining contractile function by regulating sarcomeric protein turnover [2,3].

In skeletal muscle, overexpression of Fbxl22 isoforms in mice leads to myopathy/atrophy, suggesting its role in neurogenic muscle atrophy. Knockdown of Fbxl22 in MuRF1 KO mice muscles results in significant additive muscle sparing after denervation, indicating its importance in muscle mass regulation [2]. In cardiomyocytes, targeted knockdown of Fbxl22 in rats and zebrafish embryos causes the accumulation of α-actinin, severely impaired contractile function, and cardiomyopathy [3]. Also, in zebrafish heart regeneration, blocking AP-1 function leads to decreased chromatin accessibility at the fbxl22 locus, affecting sarcomere disassembly [1].

In conclusion, Fbxl22 is essential for muscle and cardiac function. Studies using gene-knockdown and over-expression models in mice and zebrafish have revealed its role in muscle atrophy and cardiac contractility. These findings have implications for understanding muscle-related and cardiac diseases, and potentially developing therapeutic strategies for these conditions.

References:

1. Beisaw, Arica, Kuenne, Carsten, Guenther, Stefan, Looso, Mario, Stainier, Didier Y R. 2020. AP-1 Contributes to Chromatin Accessibility to Promote Sarcomere Disassembly and Cardiomyocyte Protrusion During Zebrafish Heart Regeneration. In Circulation research, 126, 1760-1778. doi:10.1161/CIRCRESAHA.119.316167. https://pubmed.ncbi.nlm.nih.gov/32312172/

2. Hughes, David C, Baehr, Leslie M, Driscoll, Julia R, Waddell, David S, Bodine, Sue C. 2020. Identification and characterization of Fbxl22, a novel skeletal muscle atrophy-promoting E3 ubiquitin ligase. In American journal of physiology. Cell physiology, 319, C700-C719. doi:10.1152/ajpcell.00253.2020. https://pubmed.ncbi.nlm.nih.gov/32783651/

3. Spaich, Sebastian, Will, Rainer D, Just, Steffen, Rottbauer, Wolfgang, Frey, Norbert. 2012. F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box protein that regulates sarcomeric protein turnover and is essential for maintenance of contractile function in vivo. In Circulation research, 111, 1504-16. doi:10.1161/CIRCRESAHA.112.271007. https://pubmed.ncbi.nlm.nih.gov/22972877/