Mustn1-KO Mouse

Mustn1, also known as Musculoskeletal embryonic nuclear protein 1 or Mustang, is a gene encoding a small nuclear protein (∼9.6 kDa) not belonging to any known family. It is highly homologous across vertebrate species and is predominantly expressed in musculoskeletal tissues like bone, cartilage, skeletal muscle, and tendon. Mustn1 is crucial for normal embryonic development, postnatal growth, exercise-related responses, and regeneration of bone and skeletal muscle. Its expression is regulated by the AP family of transcription factors, especially c-Fos, Fra-2, and JunD [2].

In skeletal muscle, Mustn1-deficient mouse models have been used to study its function. Mustn1 ablation in Pax7-positive skeletal muscle satellite cells led to functional alterations. Two-month-old Mustn1 KO mice showed an approximately 10% decrease in overall grip strength, and at 4 months, KO mice generated about 8% higher vertical force in the hindlimb. Ex-vivo experiments revealed 20-50% decreases in skeletal muscle contractions and 10-20% fatigue in the soleus of 2-and 4-month-old KO mice. Immunofluorescent analyses showed an increase in Type IIb fibers and a decrease in Type I fibers, suggesting an association with muscle fiber typing [3]. Additionally, male Mustn1 KO mice had increased glucose tolerance at 2 months, coinciding with upregulated GLUT1 and GLUT10 transporters and MUP-1, while OSTN expression was lower [4].

In conclusion, Mustn1 is a key regulatory gene in the musculoskeletal system, especially in skeletal muscle development, function, and metabolism. Studies using Mustn1 KO mouse models have revealed its role in muscle fiber differentiation, glucose metabolism, and muscle strength, providing insights relevant to muscle-wasting conditions such as muscular dystrophies [1,3,4].

References:

1. Kim, Charles J, Hadjiargyrou, Michael. 2024. Mustn1 in Skeletal Muscle: A Novel Regulator? In Genes, 15, . doi:10.3390/genes15070829. https://pubmed.ncbi.nlm.nih.gov/39062608/

2. Hadjiargyrou, Michael. 2018. Mustn1: A Developmentally Regulated Pan-Musculoskeletal Cell Marker and Regulatory Gene. In International journal of molecular sciences, 19, . doi:10.3390/ijms19010206. https://pubmed.ncbi.nlm.nih.gov/29329193/

3. Kim, Charles J, Singh, Chanpreet, Kaczmarek, Marina, Granatosky, Michael C, Hadjiargyrou, Michael. 2023. Mustn1 ablation in skeletal muscle results in functional alterations. In FASEB bioAdvances, 5, 541-557. doi:10.1096/fba.2023-00082. https://pubmed.ncbi.nlm.nih.gov/38094159/

4. Kim, Charles J, Singh, Chanpreet, Lee, Christine, Ramos, Raddy L, Hadjiargyrou, Michael. . Mustn1 ablation in skeletal muscle results in increased glucose tolerance concomitant with upregulated GLUT expression in male mice. In Physiological reports, 11, e15674. doi:10.14814/phy2.15674. https://pubmed.ncbi.nlm.nih.gov/37170065/