Maged1-KO Mouse

MAGED1, short for melanoma-associated antigen D1, is a member of the type II MAGE gene family. It is ubiquitously expressed and has diverse functions. It is involved in multiple biological processes such as neuronal apoptosis during development, regulation of the circadian clock, and anti-tumorigenesis [2].

Genetic ablation of MAGED1 in mice has shown various impacts. In pulmonary hypertension (PH), deletion of the m6A effector YTHDF1, which promotes MAGED1 translation, ameliorated PH development, suggesting MAGED1 promotes PASMC proliferation and PH [1]. In Parkinson's disease, Maged1-deficient mice had attenuated motor deficits, loss of dopaminergic neurons, and disease progression induced by MPTP, as Maged1 deficiency upregulated Akt and downregulated mTOR signaling pathways [3]. In cocaine-related behaviors, Maged1-knockout mice were insensitive to cocaine-mediated locomotor sensitization, CPP, and drug self-administration, indicating Maged1 is critical for cortico-accumbal neurotransmission [6]. In bone remodeling, Maged1-deficient mice showed an osteoporotic phenotype with increased osteoclast number and surface, and enhanced osteoblast proliferation and differentiation [4]. In learning and memory, Maged1-knockout mice had reduced basal synaptic transmission, hippocampal dysfunction, and impaired spatial learning due to the downregulated activity of CREB [5]. In skeletal myogenic differentiation, Maged1-knockout myoblasts had defective cell cycle exit and impaired myotube maturation, leading to delayed muscle regeneration [7].

In conclusion, MAGED1 is a multifunctional gene. Its knockout mouse models have revealed its significance in diseases like pulmonary hypertension, Parkinson's disease, and drug addiction, as well as in biological processes such as bone remodeling, learning and memory, and skeletal myogenic differentiation. These findings contribute to a better understanding of the underlying mechanisms and may provide potential targets for therapeutic interventions.

References:

1. Hu, Li, Wang, Jie, Huang, Huijie, Fulton, David J R, Chen, Feng. . YTHDF1 Regulates Pulmonary Hypertension through Translational Control of MAGED1. In American journal of respiratory and critical care medicine, 203, 1158-1172. doi:10.1164/rccm.202009-3419OC. https://pubmed.ncbi.nlm.nih.gov/33465322/

2. Wang, Xiaohan, Gao, Xiang, Xu, Ying. 2011. MAGED1: molecular insights and clinical implications. In Annals of medicine, 43, 347-55. doi:10.3109/07853890.2011.573806. https://pubmed.ncbi.nlm.nih.gov/21612333/

3. Wang, Jie, Xu, Sheng-Ye, Ye, Zhi-Yuan, You, Wei-Yan, Gao, Jun. 2023. The deficiency of Maged1 attenuates Parkinson's disease progression in mice. In Molecular brain, 16, 22. doi:10.1186/s13041-023-01011-3. https://pubmed.ncbi.nlm.nih.gov/36774489/

4. Liu, Mei, Xu, Lijuan, Ma, Xiao, Pan, Qiuhui, Wen, Chuanjun. 2015. MAGED1 is a negative regulator of bone remodeling in mice. In The American journal of pathology, 185, 2653-67. doi:10.1016/j.ajpath.2015.06.017. https://pubmed.ncbi.nlm.nih.gov/26272363/

5. Yang, JianJun, Lai, BeiBei, Xu, AiLi, Gao, Xiang, Gao, Jun. 2014. Maged1 co-interacting with CREB through a hexapeptide repeat domain regulates learning and memory in mice. In Molecular neurobiology, 51, 8-18. doi:10.1007/s12035-014-8677-x. https://pubmed.ncbi.nlm.nih.gov/24700102/

6. De Backer, Jean-François, Monlezun, Stéphanie, Detraux, Bérangère, Schiffmann, Serge N, de Kerchove d'Exaerde, Alban. 2018. Deletion of Maged1 in mice abolishes locomotor and reinforcing effects of cocaine. In EMBO reports, 19, . doi:10.15252/embr.201745089. https://pubmed.ncbi.nlm.nih.gov/30002119/

7. Nguyen, Tuan H N, Bertrand, Mathieu J M, Sterpin, Christiane, Achouri, Younes, De Backer, Olivier R Y. 2010. Maged1, a new regulator of skeletal myogenic differentiation and muscle regeneration. In BMC cell biology, 11, 57. doi:10.1186/1471-2121-11-57. https://pubmed.ncbi.nlm.nih.gov/20646279/