GENETIC STUDIES OF NON-ERYTHROID SPECTRIN

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Our long term goal is to define the characteristic cellular and developmental role or roles of spectrin and understand how spectrin molecules contribute to specific cellular functions. We believe our long term goal can be attained by using a model system, Drosophila melanogaster, that can be investigated at both the cellular and the tissue level using a combination of biochemical, structural and genetic approaches. Antibodies will be used to study the distribution and expression of spectrin both in cell culture and during development and to identify DNA sequences that express Drosophila spectrin. Clones of these DNA sequences will be used to map the physical location of the spectrin coding sequences on the genetic map of Drosophila and classical genetic analysis and in vitro mutant production will then be carried out. The mutants will be used to investigate spectrin function in vivo and to determine the effects of the complete absence of functional spectrin. The clones will also be used together with the technology of anti-sense inhibition of expression to inhibit spectrin expression in cultured cells so that we may probe the effects of the absence of functional spectrin or the consequences of mutant spectrin expression in cultured cells. Spectrin is present in nearly all human cells but the health consequences of defective spectrin expression have only been explored in erythrocytes. The proposed experiments should provide an in-depth understanding of spectrin's role in non- erythroid cells.