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Expression of human amyloid precursor protein in the skeletal muscles of Drosophila results in age- and activity-dependent muscle weakness
Godenschwege, Tanja A
Schwartz, Lawrence M
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.
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.
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.
amyloid precursor protein (APP); Drosophila; muscle; mitochondria; electron microscopy; apoptosis; Parkin
Bioinformatics and the Undergraduate Curriculum Essay
CBE Life Sciences Education
Recent advances involving high-throughput techniques for data generation and analysis have made familiarity with basic bioinformatics concepts and programs a necessity in the biological sciences. Undergraduate students increasingly need training in methods related to finding and retrieving information stored in vast databases. The rapid rise of bioinformatics as a new discipline has challenged many colleges and universities to keep current with their curricula, often in the face of static or dwindling resources. On the plus side, many bioinformatics modules and related databases and software programs are free and accessible online, and interdisciplinary partnerships between existing faculty members and their support staff have proved advantageous in such efforts. We present examples of strategies and methods that have been successfully used to incorporate bioinformatics content into undergraduate curricula.
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