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Association of myostatin deficiency with collagen related disease-umbilical hernia and tippy toe standing in pigs

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Abstract

Herein, we investigate the high incidence of umbilical hernia and tippy-toe standing and their underlying changes in gene expression and proliferation in myostatin knockout (MSTN−/−) pigs. Thirty-six male MSTN−/− pigs were generated by somatic cell nuclear transfer (SCNT). These pigs presented a considerably high incidence of tippy-toe standing and umbilical hernia (69.4% and 61.1%, respectively). The tendon to body weight ratio was significantly lower than wild-type pigs (0.202 ± 0.017 vs 0.250 ± 0.004, respectively). The crimp length of the MSTN−/− tendon was significantly longer than that of wild-type pigs. The expression of MSTN and the activin type IIB (ACVR2B) was detected in the tendon and linea alba of MSTN−/− pigs. MSTN treatment significantly increased the phosphorylation of Smad2/3 in both tendon and linea alba fibroblasts. Type I collagen (Col1A) and Scleraxis (Scx) expression levels in the tendon and linea alba of MSTN−/− pigs were significantly lower than those in wild-type in vivo, whereas and cyclin-dependent kinase inhibitor 1 (p21) expression levels were higher. Treatment of tendon and linea alba fibroblasts with recombinant MSTN increased Col1A and Scx and decreased p21 expression in vivo. Moreover, there was a significant increase in fibroblast proliferation after treatment. The results indicated that MSTN regulates collagen expression and proliferation in tendon and linea alba fibroblasts; thus, MSTN deficiency causes collagen-related pathological features in MSTN−/− pigs. Hence, MSTN could be used as a therapeutic target for treating UH and tendon abnormalities.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank all the staff at the Longxing Pig Farm (Longjing, China) for their assistance with feeding and care of the animals.

Funding

This work was supported by the National Natural Science Foundation of China (No. 31860297).

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  1. Hyo-Jin Paek and Zhao-Bo Luo: Joint first author.

Authors and Affiliations

  1. Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanbian University, Yanji, 133002, Jilin, China

    Hyo-Jin Paek, Zhao-Bo Luo, Hak-Myong Choe, Biao-Hu Quan, Kai Gao, Sheng-Zhong Han, Zhou-Yan Li, Jin-Dan Kang & Xi-Jun Yin

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Contributions

All authors contributed to the writing, review, and editing. H.-J. Paek contributed to conception and design of the study, writing of the manuscript; H.-J. Paek and Z.-B. Luo collected the field samples; H.-M. Choe, K. Gao, S.-Z. Han, and Z.-Y. Li performed experiments and collected the data; J.-D. Kang and B.-H. Quan analyzed the data statistically; X.-J. Yin provided regarding supervision and funding support. All authors approved the final version of the manuscript.

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Correspondence to Xi-Jun Yin.

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Paek, HJ., Luo, ZB., Choe, HM. et al. Association of myostatin deficiency with collagen related disease-umbilical hernia and tippy toe standing in pigs. Transgenic Res 30, 663–674 (2021). https://doi.org/10.1007/s11248-021-00275-6

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