Lessons from Animal Models of Cytoplasmic Intermediate Filament Proteins

  • Jamal-Eddine BouameurEmail author
  • Thomas M. MaginEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 82)


Cytoplasmic intermediate filaments (IFs) represent a major cytoskeletal network contributing to cell shape, adhesion and migration as well as to tissue resilience and renewal in numerous bilaterians, including mammals. The observation that IFs are dispensable in cultured mammalian cells, but cause tissue-specific, life-threatening disorders, has pushed the need to investigate their function in vivo. In keeping with human disease, the deletion or mutation of murine IF genes resulted in highly specific pathologies. Epidermal keratins, together with desmin, are essential to protect corresponding tissues against mechanical force but also participate in stabilizing cell adhesion and in inflammatory signalling. Surprisingly, other IF proteins contribute to tissue integrity to a much lesser extent than anticipated, pointing towards their role in stress situations. In support, the overexpression of small chaperones or the interference with inflammatory signalling in several settings has been shown to rescue severe tissue pathologies that resulted from the expression of mutant IF proteins. It stills remains an open issue whether the wide range of IF disorders share similar pathomechanisms. Moreover, we lack an understanding how IF proteins participate in signalling processes. Now, with a large number of mouse models in hand, the next challenge will be to develop organotypic cell culture models to dissect pathomechanisms at the molecular level, to employ Crispr/Cas-mediated genome engineering to optimize models and, finally, to combine available animal models with medicinal chemistry for the development of molecular therapies.


Intermediate filaments Keratins Epithelia Vimentin Desmin GFAP Peripherin Syncoilin Neurofilaments α-internexin Nestin Synemin Phakinin Filensin Animal models 

List of Abbreviations


adenosine monophosphate


adenosine triphosphate


Alexander disease


basal cell carcinoma


cystic fibrosis transmembrane conductance regulator


danger-associated molecular patterns


embryonic day


epidermolysis bullosa simplex


enhanced green fluorescent protein


glial fibrillary acidic protein


glucose transporter


intermediate filament








knock in


knock out


keratin type I


keratin type II


Mallory-Denk bodies


Meesmann epithelial corneal dystrophy


major histocompatibility complex




nuclear factor-kappa B


reactive oxygen species




tumour necrosis factor


tumour necrosis factor receptor




thymic stromal lymphopoietin


wild type



Work in the Magin lab is supported by the DFG (MA1316-15, MA1316-17, MA1316-19, MA1316-21, INST 268/230-1). The authors declare no competing financial interests. For the figure, some illustrations were taken from somersault18:24 website (license: Attribution-NonCommercial-ShareAlike 4.0 International, CC BY-NC-SA 4.0).


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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Sächsischer Inkubator für Klinische Translation (SIKT) & Institute of Biology Division of Cell and Developmental BiologyUniversity of LeipzigLeipzigGermany

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