- 作者: Aseervatham Anusha Amali; Cliff Ji-Fan Lin; Yi-Hsuan Chen; Wei-Lun Wang; Hong-Yi Gong; Ravikumar Deepa Rekha;Jenn-Kan Lu; Thomas T. Chen; Jen-Leih Wu
- 作者服務機構: Laboratory of Marine Molecular Biology and Biotechnology,Institute of Cellular and Organismic Biology, AcademiaSinica, Taiwan; Graduate Institute of Life Sciences, National Defense MedicalCenter, Taipei, Taiwan; Institute of Fisheries Science, National Taiwan University,Taipei, Taiwan
- 中文摘要: --
- 英文摘要: Myostatin, a member of the TGF-b superfamily,is a potent negative regulator of skeletal muscle andgrowth. Previously, we reported Mstn1 from zebrafish andstudied its influence on muscle development. In this study,we identified another form of Myostatin protein which isreferred to as Mstn2. The size of Mstn2 cDNA is 1342 bpwith 109 and 132 bp of 50 and 30-untranslated regions(UTRs), respectively. The coding region is 1101 bpencoding 367 amino acids. The identity between zebrafishMstn1 and 2 is 66%. The phylogenetic tree revealed thatthe Mstn2 is an ancestral form of Mstn1. To study thefunctional aspects, we overexpressed mstn2 and noticedthat embryos became less active and the juveniles with bentand curved phenotypes when compared to the control. TheRT-PCR and in situ hybridization showed concurrentreduction of dystrophin associated protein complex(DAPC). In cryosection and in situ hybridization, weobserved the disintegration of somites, lack of transversemyoseptum and loss of muscle integrity due to the failureof muscle attachment in mstn2 overexpressed embryos.Immunohistochemistry and western blot showed that therewas a reduction of dystrophin, dystroglycan and sarcoglycanat translational level in overexpressed embryos. Takentogether, these results indicate the suitability of zebrafish asan excellent animal model and our data provide the firstin vivo evidence of muscle attachment failure by theoverexpression of mstn2 and it leads to muscle losswhich results in muscle dystrophy that may contribute toDuchenne syndrome and other muscle related diseases.
- 中文關鍵字: --
- 英文關鍵字: Myostatin; Muscle attachment; Muscular dystrophy; DAPC; Muscle development