Vector-borne diseases continue to cause significant mortality and morbidity in people throughout the world. While malaria and yellow fever are scourges of lesser-developed countries, the threat of Dengue fever is at the borders of the United States. Control of transmission of these diseases can be achieved by controlling their insect vectors. The development of mosquito transgenesis has made possible the producion of mosquitoes that have been altered by the stable insertion of exogenous genes. Our long-term goal is to produce transgenic mosquitoes that are resistant to infection by pathogens and use these as systems for studying pathogen-vector interactions as well as release organisms for programs seeking genetic control over the transmission of parasitic and viral diseases. Furthermoe, transormation makes it possible to study biochemical and molecular biological processes involved in basic aspects of mosuito physiology such as blood feeding and digestion, oogenesis and host seeking. Transposon-based genetic analysis of mosquitoes has the potential to identify many crucial genes whose expression is important for vector competence and vectorial capacity. Recently, we have shown that twso Class II transposable elements, Hermes and mariner, mediate the insertion of exogenous DNA into the chromosomes of the yellow fever mosquito. Aedes egypti (Jasinskiene et al., 1998; Coates et al., 1998). Further refinements of these transformation systems are reuqired to facilitate their use in producing pathogen- resistant mosquitoes and other strains for basic biological study.Towards these ends we propose the following specific aims: 1) develop methods for routine isolation of DNA fragments consisting of transposon-chromosome junctions from Hermes-transformed mosquito lines; 2) develop procedures and strains for remobilization of Hermes and Mariner chromosomal insertions; 3) produce transgenic strains of mosquitoes that exploit cre-loxp and FLP-FRT site-specific recombination for comparative promoter analysis. Successful accomplishment of these Specific Aim will result in robust and widely-applicable systems or mosquito transgenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI044238-01
Application #
2742511
Study Section
Special Emphasis Panel (ZRG5-TMP (01))
Program Officer
Aultman, Kathryn S
Project Start
1998-12-01
Project End
2003-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Juhn, J; Marinotti, O; Calvo, E et al. (2008) Gene structure and expression of nanos (nos) and oskar (osk) orthologues of the vector mosquito, Culex quinquefasciatus. Insect Mol Biol 17:545-52
Terenius, Olle; Marinotti, Osvaldo; Sieglaff, Douglas et al. (2008) Molecular genetic manipulation of vector mosquitoes. Cell Host Microbe 4:417-23
Adelman, Zach N; Jasinskiene, Nijole; Onal, Sedef et al. (2007) nanos gene control DNA mediates developmentally regulated transposition in the yellow fever mosquito Aedes aegypti. Proc Natl Acad Sci U S A 104:9970-5
Juhn, J; James, A A (2006) oskar gene expression in the vector mosquitoes, Anopheles gambiae and Aedes aegypti. Insect Mol Biol 15:363-72
Calvo, Eric; Walter, Marika; Adelman, Zachary N et al. (2005) Nanos (nos) genes of the vector mosquitoes, Anopheles gambiae, Anopheles stephensi and Aedes aegypti. Insect Biochem Mol Biol 35:789-98
Adelman, Zach N; Jasinskiene, Nijole; Vally, K J M et al. (2004) Formation and loss of large, unstable tandem arrays of the piggyBac transposable element in the yellow fever mosquito, Aedes aegypti. Transgenic Res 13:411-25
Jasinskiene, Nijole; Coates, Craig J; Ashikyan, Aurora et al. (2003) High efficiency, site-specific excision of a marker gene by the phage P1 cre-loxP system in the yellow fever mosquito, Aedes aegypti. Nucleic Acids Res 31:e147
James, A A (2002) Engineering mosquito resistance to malaria parasites: the avian malaria model. Insect Biochem Mol Biol 32:1317-23
Atkinson, Peter W; James, Anthony A (2002) Germline transformants spreading out to many insect species. Adv Genet 47:49-86
Coates, C J; Jasinskiene, N; Morgan, D et al. (2000) Purified mariner (Mos1) transposase catalyzes the integration of marked elements into the germ-line of the yellow fever mosquito, Aedes aegypti. Insect Biochem Mol Biol 30:1003-8

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