The fibrous form of intracellular inclusion bodies in recombinant variant fibrinogen-producing cells is specific to the hepatic fibrinogen storage disease-inducible variant fibrinogen

Int J Hematol. 2017 Jun;105(6):758-768. doi: 10.1007/s12185-017-2185-5. Epub 2017 Feb 4.


Fibrinogen storage disease (FSD) is a rare disorder that is characterized by the accumulation of fibrinogen in hepatocytes and induces liver injury. Six mutations in the γC domain (γG284R, γT314P, γD316N, the deletion of γG346-Q350, γG366S, and γR375W) have been identified for FSD. Our group previously established γ375W fibrinogen-producing Chinese hamster ovary (CHO) cells and observed aberrant large granular and fibrous forms of intracellular inclusion bodies. The aim of this study was to investigate whether fibrous intracellular inclusion bodies are specific to FSD-inducible variant fibrinogen. Thirteen expression vectors encoding the variant γ-chain were stably or transiently transfected into CHO cells expressing normal fibrinogen Aα- and Bβ-chains or HuH-7 cells, which were then immunofluorescently stained. Six CHO and HuH-7 cell lines that transiently produced FSD-inducible variant fibrinogen presented the fibrous (3.2-22.7 and 2.1-24.5%, respectively) and large granular (5.4-25.5 and 7.7-23.9%) forms of intracellular inclusion bodies. Seven CHO and HuH-7 cell lines that transiently produced FSD-non-inducible variant fibrinogen only exhibit the large granular form. These results demonstrate that transiently transfected variant fibrinogen-producing CHO cells and inclusion bodies of the fibrous form may be useful in non-invasive screening for FSD risk factors for FSD before its onset.

Keywords: Fibrinogen storage disease; Hypofibrinogenemia; Immunofluorescence; Intracellular inclusion bodies; Recombinant fibrinogen.

MeSH terms

  • Amino Acid Substitution
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Fibrinogen* / genetics
  • Fibrinogen* / metabolism
  • Hepatocytes* / metabolism
  • Hepatocytes* / pathology
  • Humans
  • Inclusion Bodies* / genetics
  • Inclusion Bodies* / metabolism
  • Inclusion Bodies* / pathology
  • Liver Diseases* / genetics
  • Liver Diseases* / metabolism
  • Liver Diseases* / pathology
  • Mutation, Missense*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism


  • Recombinant Proteins
  • Fibrinogen