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Lessons from Animal Models of Cytoplasmic Intermediate Filament Proteins

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

Abstract

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.

Keywords

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

List of Abbreviations

AMP

adenosine monophosphate

ATP

adenosine triphosphate

AxD

Alexander disease

BCC

basal cell carcinoma

CFTR

cystic fibrosis transmembrane conductance regulator

DAMPs

danger-associated molecular patterns

E

embryonic day

EBS

epidermolysis bullosa simplex

EGFP

enhanced green fluorescent protein

GFAP

glial fibrillary acidic protein

GLUT

glucose transporter

IF

intermediate filament

IFN

interferon

IL-

interleukin-

K

keratin

KI

knock in

KO

knock out

KtyI

keratin type I

KtyII

keratin type II

MDBs

Mallory-Denk bodies

MECD

Meesmann epithelial corneal dystrophy

MHC

major histocompatibility complex

NF-

neurofilament-

NF-κB

nuclear factor-kappa B

ROS

reactive oxygen species

Tg

transgenic

TNF

tumour necrosis factor

TNFR

tumour necrosis factor receptor

TPA

12-O-tetradecanoylphorbol-13-acetate

TSLP

thymic stromal lymphopoietin

WT

wild type

Notes

Acknowledgments

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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