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Modeling Familial Amyloidotic Polyneuropathy (Transthyretin V30M) in Drosophila melanogaster
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Clinical and Experimental Medicine, Developmental Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Physics, Chemistry and Biology, Biochemistry. Linköping University, The Institute of Technology.
2009 (English)In: NEURODEGENERATIVE DISEASES, ISSN 1660-2854, Vol. 6, no 3, 127-138 p.Article in journal (Refereed) Published
Abstract [en]

Background/Aims: Transthyretin (TTR) is a prevalent plasma and cerebrospinal fluid protein associated with sporadic and heritable amyloidosis. TTR amyloidosis is linked to a vast number of mutations with varying phenotype, tissue distribution and age of onset. The most prevalent mutation associated with familial amyloidotic polyneuropathy (FAP) is the V30M mutation. Studies of transgenic mouse models of TTR V30M FAP have been hampered by variable phenotype, low disease penetrance, and slow onset. Methods/Results: To model TTR-associated amyloid disease in the Drosophila model system, transgenic Drosophila were generated, expressing wild-type (wt) TTR or TTR V30M, associated with sporadic senile systemic amyloidosis (SSA) and inherited FAP, respectively. We found that expression of FAP-associated TTR V30M mutant in the nervous system resulted in reduced lifespan and in reduced climbing ability indicating neurological impairment, whereas expression of TTR wt showed a milder phenotype. Congo red staining of the Drosophila brain shows positive amyloid binding in the aged TTR V30M flies. Extensive brain vacuole formation was evident for the aged TTR V30M flies, whereas a milder phenotype was shown by the TTR wt flies. In addition, expression of TTR V30M in the eye leads to tissue damage, including rough eye, morphological changes and fibrous deposition. Conclusion: Our results suggest that Drosophila is a promising complementary system for studies of TTR-associated amyloid diseases.

Place, publisher, year, edition, pages
2009. Vol. 6, no 3, 127-138 p.
Keyword [en]
Amyloid disease, Drosophila melanogaster, Transthyretin, Familial amyloidotic polyneuropathy
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-18382DOI: 10.1159/000213761OAI: diva2:218870
Available from: 2009-05-25 Created: 2009-05-25 Last updated: 2015-05-28
In thesis
1. Modeling Amyloid Disease in Drosophila melanogaster
Open this publication in new window or tab >>Modeling Amyloid Disease in Drosophila melanogaster
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Amyloid diseases are caused by protein misfolding and aggregation. To date there are 27 known proteins causing amyloid disorders involving brain and peripheral protein deposition. The proteins involved in this mechanism do not share sequence homology, but the amyloid fibrils share biophysical properties and possibly a common pathogenic mechanism. Amyloid deposits are known to be involved in a broad range of neurodegenerative diseases, such as Alzheimer’s disease and Creutzfeldt-Jakob disease, as well as in non-neuropathic diseases, such as senile systemic amyloidosis and type II diabetes.

During the last decade the fruit fly, Drosophila melanogaster (Drosophila), have increasingly been used as a model for neurodegenerative disease, such as Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and familial amyloidotic polyneuropathy. The advantages of using the Drosophila model are the well-defined genetic characteristics, the quantity, short life span, simplicity in genetic manipulation and the powerful binary UAS-Gal4 transgenic system. The UAS-Gal4 system allows for rapid generation of individual strains in which expression of a specific gene of interest can be directed to different tissues or cell types. The system allows the target gene to be activated in different cell- and tissue-types by altering the activator-expressing lines.

This thesis has been focused on modeling amyloid diseases in Drosophila. This has been performed by:

  • Creating new model systems of senile systemic amyloidosis and familial amyloidotic polyneuropathy in Drosophila
  • Developing a new staining protocol for detection of amyloid in Drosophila
  • Initiate a compound screen of Alzheimer’s disease modeled in Drosophila
Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 88 p.
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1320
National Category
Natural Sciences
urn:nbn:se:liu:diva-55025 (URN)978-91-7393-379-7 (ISBN)
Public defence
2010-05-21, Planck, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 09:15 (English)
Available from: 2010-04-27 Created: 2010-04-27 Last updated: 2010-04-27Bibliographically approved

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Berg, InaThor, StefanHammarström, Per
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