RRC ID 65925
Author Arai S, Ogiwara N, Mukai S, Takezawa Y, Sugano M, Honda T, Okumura N.
Title The fibrous form of intracellular inclusion bodies in recombinant variant fibrinogen-producing cells is specific to the hepatic fibrinogen storage disease-inducible variant fibrinogen.
Journal Int J Hematol
Abstract 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.
Volume 105(6)
Pages 758-768
Published 2017-6-1
DOI 10.1007/s12185-017-2185-5
PII 10.1007/s12185-017-2185-5
PMID 28161763
MeSH 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
IF 2.245
Human and Animal Cells HuH-7(RCB1942)