title: Small interfering RNA (siRNA)-mediated knockdown of myostatin influences the expression of myogenic regulatory factors in caprine foetal myoblasts.
abstract: Myostatin (MSTN) acts as a negative regulator of skeletal muscle development. Naturally occurring inactivating mutations in the coding region and knockout as well as knockdown of MSTN result in an increase in the muscle mass. However, the effect of MSTN knockdown on the expression of myogenic regulatory factors (MRFs) has not been studied in farm animals including goats. In the present study, using different synthetic siRNAs (n = 3), we demonstrated as high as 69 (p < 0.01) and 89% downregulation of MSTN mRNA and protein in the primary caprine foetal myoblast cells. Further, we also examined the effect of MSTN knockdown on the transcripts of MRFs including MyoD, Myf5 and MYOG. The expression of Myf5 remained unaffected (p = 0.60); however, MSTN downregulation caused a significant (p < 0.05) decrease and increase of MYOG and MyoD expression, respectively. Assessment of OAS1 expression confirmed the absence of any siRNA-elicited interferon response. Our results demonstrate that the downregulation of MSTN expression was accompanied by differential expressions of MRFs without any adverse interferon response. This study also suggests the importance of siRNA-mediated knockdown of MSTN as a potential alternative to increase muscle mass and meat production.
authors.affiliation: Genome Analysis Laboratory, Animal Genetics Division, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243122, India.
authors.forename: Rohit
authors.initials: R
authors.lastname: Kumar
authors.forename: Satyendra Pal
authors.initials: SP
authors.lastname: Singh
authors.forename: Priya
authors.initials: P
authors.lastname: Kumari
authors.forename: Abhijit
authors.initials: A
authors.lastname: Mitra
mesh_terms: D000818:Animals; D047108:Embryonic Development; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006041:Goats / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D032446:Myoblasts / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000096:biosynthesis / Q000235:genetics*; D055435:Myostatin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*
chemical_list: D018006:Myogenic Regulatory Factors; D055435:Myostatin; D012333:RNA, Messenger; D034741:RNA, Small Interfering