IGFN1_v1 is required for myoblast fusion and differentiation

PLoS One. 2017 Jun 30;12(6):e0180217. doi: 10.1371/journal.pone.0180217. eCollection 2017.


Igfn1 is a complex locus that codes for multiple splicing variants of Immunoglobulin- and Fibronectin-like domain containing proteins predominantly expressed in skeletal muscle. To reveal possible roles for Igfn1, we applied non-selective knock-down by shRNAs as well as specific targeting of Igfn1 exon 13 by CRISPR/Cas9 mutagenesis in C2C12 cells. Decreased expression of Igfn1 variants via shRNAs against the common 3'-UTR region caused a total blunting of myoblast fusion, but did not prevent expression of differentiation markers. Targeting of N-terminal domains by elimination of exon 13 via CRISPR/Cas9 mediated homologous recombination, also resulted in fusion defects as well as large multinucleated cells. Expression of IGFN1_v1 partially rescued fusion and myotube morphology in the Igfn1 exon 13 knock-out cell line, indicating a role for this variant in myoblast fusion and differentiation. However, in vivo overexpression of IGFN1_v1 or the Igfn1 Exon 13 CRISPR/Cas9 targeting vector did not result in significant size changes in transfected fibres.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Base Sequence
  • Cell Differentiation / physiology*
  • Cell Fusion*
  • Cell Line
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • Exons
  • Homologous Recombination
  • Mice
  • Muscle, Skeletal / cytology*
  • Myoblasts / cytology*
  • Proteins / genetics
  • Proteins / physiology*


  • Adaptor Proteins, Signal Transducing
  • Igfn1 protein, mouse
  • Proteins

Grant support

Support was provided by the Medical Research Council (MC_U142684168 to Andy Haynes) and Biotechnology and Biological Sciences Research Council (BB/M011151/1 to Tobias Cracknell).