Myod1-KO Mouse

Myod1, a member of the MyoD1 family of myogenic nuclear regulatory proteins, is a pivotal transcription factor during myogenesis [3]. It is critical for skeletal muscle development, promoting the expression of muscle-specific genes [5]. Myod1 binds to numerous skeletal muscle enhancers in collaboration with the glucocorticoid receptor (GR) to control gene expression, and this regulation occurs through direct contacts with the promoter region of target genes, via the CpG-bound transcription factor Nrf1, and the formation of Ctcf-anchored chromatin loops, in a myofiber-specific manner [2].

In rhabdomyosarcoma (RMS), Myod1 is expressed, and its lack of immunoreactivity in non-alveolar RMS (non-ARMS) is associated with poor prognosis, especially in embryonal (ERMS) and spindle cell sclerosing RMS (SRMS). MYOD1 gene mutations are generally infrequent in pediatric RMS, but when present, they can define an aggressive RMS subset, with poor outcome and response to therapy, irrespective of age [1,6]. In gastric cancer, MyoD1 inhibits cell proliferation, migration, and invasion. It promotes the transcription of BIK and inhibits the transcription of FUT4, affecting cancer-related signaling pathways [4,5].

In conclusion, Myod1 is essential for skeletal muscle development and exerts significant impacts on the development of certain cancers, such as rhabdomyosarcoma and gastric cancer. The study of Myod1 in genetic models helps to understand its role in normal muscle development and disease-related biological processes, providing potential directions for diagnosis, prognosis, and treatment of related diseases.

References:

1. Ahmed, Atif A, Habeebu, Sultan, Farooqi, Midhat S, Barr, Frederic G, Tsokos, Maria G. 2021. MYOD1 as a prognostic indicator in rhabdomyosarcoma. In Pediatric blood & cancer, 68, e29085. doi:10.1002/pbc.29085. https://pubmed.ncbi.nlm.nih.gov/33913590/

2. Rovito, Daniela, Rerra, Anna-Isavella, Ueberschlag-Pitiot, Vanessa, Duteil, Delphine, Metzger, Daniel. . Myod1 and GR coordinate myofiber-specific transcriptional enhancers. In Nucleic acids research, 49, 4472-4492. doi:10.1093/nar/gkab226. https://pubmed.ncbi.nlm.nih.gov/33836079/

3. Folpe, Andrew L. . MyoD1 and myogenin expression in human neoplasia: a review and update. In Advances in anatomic pathology, 9, 198-203. doi:. https://pubmed.ncbi.nlm.nih.gov/11981115/

4. Wu, Fei, Zhang, Jinyuan, Jiang, Qiuyu, Huang, Chen, Zhang, Shuqun. 2024. MyoD1 promotes the transcription of BIK and plays an apoptosis-promoting role in the development of gastric cancer. In Cell cycle (Georgetown, Tex.), 23, 573-587. doi:10.1080/15384101.2024.2348344. https://pubmed.ncbi.nlm.nih.gov/38701194/

5. Wu, Fei, Qin, Yannan, Jiang, Qiuyu, Zhang, Shuqun, Huang, Chen. 2019. MyoD1 suppresses cell migration and invasion by inhibiting FUT4 transcription in human gastric cancer cells. In Cancer gene therapy, 27, 773-784. doi:10.1038/s41417-019-0153-3. https://pubmed.ncbi.nlm.nih.gov/31831855/

6. Agaram, Narasimhan P, LaQuaglia, Michael P, Alaggio, Rita, Wexler, Leonard H, Antonescu, Cristina R. 2018. MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma: an aggressive subtype irrespective of age. A reappraisal for molecular classification and risk stratification. In Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 32, 27-36. doi:10.1038/s41379-018-0120-9. https://pubmed.ncbi.nlm.nih.gov/30181563/