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BMC Physiology
Published in: BMC Physiology 1/2011

Open Access 01-12-2011 | Research article

Expression of human amyloid precursor protein in the skeletal muscles of Drosophila results in age- and activity-dependent muscle weakness

Authors: Chul Kim, Sapeckshita Srivastava, Marian Rice, Tanja A Godenschwege, Brooke Bentley, Saranya Ravi, Shuang Shao, Craig T Woodard, Lawrence M Schwartz

Published in: BMC Physiology | Issue 1/2011

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Abstract

Background

One of the hallmarks of Alzheimer's disease, and several other degenerative disorders such as Inclusion Body Myositis, is the abnormal accumulation of amyloid precursor protein (APP) and its proteolytic amyloid peptides. To better understand the pathological consequences of inappropriate APP expression on developing tissues, we generated transgenic flies that express wild-type human APP in the skeletal muscles, and then performed anatomical, electrophysiological, and behavioral analysis of the adults.

Results

We observed that neither muscle development nor animal longevity was compromised in these transgenic animals. However, human APP expressing adults developed age-dependent defects in both climbing and flying. We could advance or retard the onset of symptoms by rearing animals in vials with different surface properties, suggesting that human APP expression-mediated behavioral defects are influenced by muscle activity. Muscles from transgenic animals did not display protein aggregates or structural abnormalities at the light or transmission electron microscopic levels. In agreement with genetic studies performed with developing mammalian myoblasts, we observed that co-expression of the ubiquitin E3 ligase Parkin could ameliorate human APP-induced defects.

Conclusions

These data suggest that: 1) ectopic expression of human APP in fruit flies leads to age- and activity-dependent behavioral defects without overt changes to muscle development or structure; 2) environmental influences can greatly alter the phenotypic consequences of human APP toxicity; and 3) genetic modifiers of APP-induced pathology can be identified and analyzed in this model.
Appendix
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Metadata
Title
Expression of human amyloid precursor protein in the skeletal muscles of Drosophila results in age- and activity-dependent muscle weakness
Authors
Chul Kim
Sapeckshita Srivastava
Marian Rice
Tanja A Godenschwege
Brooke Bentley
Saranya Ravi
Shuang Shao
Craig T Woodard
Lawrence M Schwartz
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Physiology / Issue 1/2011
Electronic ISSN: 1472-6793
DOI
https://doi.org/10.1186/1472-6793-11-7

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