Gdf11-KO Mouse

Gdf11, also known as bone morphogenetic protein 11 (BMP11), is a member of the Transforming Growth Factor β superfamily. It plays crucial roles in embryogenesis, cell cycle control, apoptosis, and is involved in processes like lipid metabolism, inflammation, and aging. It mainly targets cells with stemness features, guiding cell differentiation and maturation [1,5,7].

In mice, selective knockout of Gdf11 in post-mitotic excitatory neurons (ENs) leads to brain aging-related transcriptional changes, EN senescence, hyperexcitability, dendritic pruning, impaired synaptic input, memory deficits, and a shortened lifespan, indicating its role in slowing EN senescence and brain aging [2]. Systemic Gdf11 administration in aged mice improves memory, alleviates senescence and depression-like symptoms through autophagy-related mechanisms, and low Gdf11 levels are seen in sera from young adults with major depressive disorder (MDD) [3]. In diabetic mice, topical Gdf11 promotes wound healing by stimulating endothelial progenitor cell mobilization and neovascularization via the HIF-1ɑ-VEGF/SDF-1ɑ pathway, and silencing Gdf11 in healthy mice mimics non-healing diabetic wounds [4]. In Gdf11 conditional knockout mouse models of osteoarthritis, loss of Gdf11 leads to NLRP3 inflammasome activation, inflammation, and metabolic dysfunction, while intra-articular administration of recombinant Gdf11 alleviates the disease pathogenesis [6].

In conclusion, Gdf11 is essential in multiple biological processes. Studies using gene knockout and conditional knockout mouse models have revealed its significance in brain aging, mood disorders, wound healing, and osteoarthritis. These models provide valuable insights into Gdf11's functions, helping to understand disease mechanisms and potentially identify new therapeutic strategies for related diseases.

References:

1. Król, Wojciech, Machelak, Weronika, Zielińska, Marta. 2023. GDF11 as a friend or an enemy in the cancer biology? In Biochimica et biophysica acta. Reviews on cancer, 1878, 188944. doi:10.1016/j.bbcan.2023.188944. https://pubmed.ncbi.nlm.nih.gov/37356738/

2. Wang, Di-Xian, Dong, Zhao-Jun, Deng, Sui-Xin, Shu, Yousheng, Zhao, Jing-Wei. 2023. GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21. In Nature communications, 14, 7476. doi:10.1038/s41467-023-43292-1. https://pubmed.ncbi.nlm.nih.gov/37978295/

3. Moigneu, Carine, Abdellaoui, Soumia, Ramos-Brossier, Mariana, Lledo, Pierre-Marie, Katsimpardi, Lida. 2023. Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy. In Nature aging, 3, 213-228. doi:10.1038/s43587-022-00352-3. https://pubmed.ncbi.nlm.nih.gov/37118117/

4. Zhang, Ying, Zhang, Yi-Yuan, Pan, Zhen-Wei, Jiao, Lei, Yang, Bao-Feng. 2022. GDF11 promotes wound healing in diabetic mice via stimulating HIF-1ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization. In Acta pharmacologica Sinica, 44, 999-1013. doi:10.1038/s41401-022-01013-2. https://pubmed.ncbi.nlm.nih.gov/36347996/

5. Machelak, Weronika, Szczepaniak, Adrian, Jacenik, Damian, Zielińska, Marta. 2023. The role of GDF11 during inflammation - An overview. In Life sciences, 322, 121650. doi:10.1016/j.lfs.2023.121650. https://pubmed.ncbi.nlm.nih.gov/37011872/

6. Zhang, Pengfei, Zhai, Haoxin, Zhang, Shuai, Zhao, Yunpeng, Zhang, Lei. 2024. GDF11 protects against mitochondrial-dysfunction-dependent NLRP3 inflammasome activation to attenuate osteoarthritis. In Journal of advanced research, , . doi:10.1016/j.jare.2024.08.001. https://pubmed.ncbi.nlm.nih.gov/39103049/

7. Simoni-Nieves, Arturo, Gerardo-Ramírez, Monserrat, Pedraza-Vázquez, Gibrán, Gomez-Quiroz, Luis E, Gutiérrez-Ruiz, María Concepción. 2019. GDF11 Implications in Cancer Biology and Metabolism. Facts and Controversies. In Frontiers in oncology, 9, 1039. doi:10.3389/fonc.2019.01039. https://pubmed.ncbi.nlm.nih.gov/31681577/