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Desmin L345P transgenic mice exhibit morphological and biochemical features of amyloidosis of two distinct types
Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
Almazov Federal Centre of Heart, Blood and Endocrinology, St. Petersburg, Russian Federation.
Karolinska Institute, Stockholm, Sweden.
Almazov Federal Centre of Heart, Blood and Endocrinology, St. Petersburg, Russian Federation.
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2010 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 31, no Suppl. 1, 924-925 p.Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Being a chief intermediate filament of the muscle tissue, desmin isimplicated in the sarcomeric organization, organelle positioning and mitochondrialfunction. Various desmin mutations have been reported as a possible cause forcardiomyopathies. Several reports on transgenic mice expressing mutant desminshowed deleterious effects of mutant desmin incorporated into filaments on cardiomyocyte function, but most importantly that accumulation of unfolded proteinaggregates plays an important pathogenic role in development of desminassociatedcardiomyopathies. Thus, in desmin transgenic mice with the L345Pmutation, which interferes in a dominant-negative manner with desmin polymerization,the accumulation of intracellular and extracellular amyloidogenic proteinaggregates was shown to be the key feature along with alteration of mitochondrialstructure and function. Therefore, the aim of this study was to characterizethe nature of amyloidogenic protein aggregates in L345P desmin transgenic miceon molecular and protein level.

Material and methods: L345P desmin transgenic mice (DM) and WT mice 40weeks old were analyzed. Myocardial cryostat 10 micron sections were stainedwith conventional techniques (hematoxilin-eosin, Congo Red). A detailed amyloidcharacterization was carried out using novel optical probes called luminescentconjugated oligothiophenes and polythiophenes (LCOs and LCPs) that specificallystain various protein aggregates and give rise to conformation dependentemission spectra.

Results: The most prominent feature of DM mice myocardium was misfoldedprotein depositions in perivascular space and between muscle fibers. Analysisof samples from DM mouse stained with LCO or LCP revealed the presence ofaggregates emitting light with two different emission spectra. Since the spectralproperties of the LCOs or LCPs are dependent on their conformation, the appearanceof two dissimilar emission spectra indicates that the probes might bindto two different types of amyloid aggregates within the tissue. Interestingly, aggregateswith emission spectra similar to one of the two types found in the DMmouse could also be found in WT mice, but in a much lower extent, suggesting asporadic cardiac amyloid pathology in C57 Bl/6 mice at 40 weeks, probably, as anative aging attribute.

Conclusions: The L345P desmin mutation causes focal amyloid protein depositionin heart muscle of two distinct types. White first one can be a natural attributeof C57 Bl/6 mice detected with age, another one can be specifically responsiblefor the development of desmin-related cardiomyopathy.

Place, publisher, year, edition, pages
Oxford, UK: Oxford University Press, 2010. Vol. 31, no Suppl. 1, 924-925 p.
National Category
Engineering and Technology
URN: urn:nbn:se:liu:diva-67388DOI: 10.1093/eurheartj/ehq290ISI: 000281531906186OAI: diva2:409677
ESC Congress 2010, Stockholm, Sweden, 28 August–1 September 2010
Available from: 2011-04-11 Created: 2011-04-11 Last updated: 2014-04-08Bibliographically approved

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Klingstedt, TheréseNilsson, PeterHammarström, Per
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