uptake of aggregating transthyretin by fat body in a drosophila model for ttr-associated amyloidosis吸收脂肪体聚合转体基因的果蝇模型ttr-associated淀粉样变.pdfVIP

Uptake of Aggregating Transthyretin by Fat Body in a Drosophila Model for TTR-Associated Amyloidosis 1,2 1 1 1,3 1 Malgorzata Pokrzywa *, Ingrid Dacklin , Monika Vestling , Dan Hultmark , Erik Lundgren , Rafael Cantera4,5 ˚ ˚ 1 Department of Molecular Biology, Umea University, Umea, Sweden, 2 Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden, 3 Institute of Medical Technology, University of Tampere, Tampere, Finland, 4 Department of Zoology, Stockholm University, Stockholm, Sweden, 5 Developmental ´ Neurobiology, Instituto de Investigaciones Biologicas Clemente Estable (IIBCE), Montevideo, Uruguay Abstract Background: A functional link has been established between the severe neurodegenerative disorder Familial amyloidotic polyneuropathy and the enhanced propensity of the plasma protein transthyretin (TTR) to form aggregates in patients with single point mutations in the TTR gene. Previous work has led to the establishment of an experimental model based on transgenic expression of normal or mutant forms of human TTR in Drosophila flies. Remarkably, the severity of the phenotype was greater in flies that expressed a single copy than with two copies of the mutated gene. Methodology/Principal Findings: In this study, we analyze the distribution of normal and mutant TTR in transgenic flies, and the ultrastructure of TTR-positive tissues to clarify if aggregates and/or amyloid filaments are formed. We report the formation of intracellular aggregates of 20 nm spherules and amyloid filaments in thorac