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Open Access Highly Accessed Research article

The vasa regulatory region mediates germline expression and maternal transmission of proteins in the malaria mosquito Anopheles gambiae: a versatile tool for genetic control strategies

Philippos A Papathanos1, Nikolai Windbichler1, Miriam Menichelli1, Austin Burt2 and Andrea Crisanti1*

Author Affiliations

1 Imperial College London, Division of Cell and Molecular Biology, Imperial College Road, London SW7 2AZ, UK

2 Dept of Biology and Centre for Population Biology, Imperial College London, Silwood Park, Ascot, Berks, SL5 7PY, UK

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BMC Molecular Biology 2009, 10:65  doi:10.1186/1471-2199-10-65

Published: 2 July 2009

Abstract

Background

Germline specific promoters are an essential component of potential vector control strategies which function by genetic drive, however suitable promoters are not currently available for the main human malaria vector Anopheles gambiae.

Results

We have identified the Anopheles gambiae vasa-like gene and found its expression to be specifically localized to both the male and female gonads in adult mosquitoes. We have functionally characterised using transgenic reporter lines the regulatory regions required for driving transgene expression in a pattern mirroring that of the endogenous vasa locus. Two reporter constructs indicate the existence of distinct vasa regulatory elements within the 5' untranslated regions responsible not only for the spatial and temporal but also for the sex specific germline expression. vasa driven eGFP expression in the ovary of heterozygous mosquitoes resulted in the progressive accumulation of maternal protein and transcript in developing oocytes that were then detectable in all embryos and neonatal larvae.

Conclusion

We have characterized the vasa regulatory regions that are not only suited to drive transgenes in the early germline of both sexes but could also be utilized to manipulate the zygotic genome of developing embryos via maternal deposition of active molecules. We have used computational models to show that a homing endonuclease-based gene drive system can function in the presence of maternal deposition and describe a novel non-invasive control strategy based on early vasa driven homing endonuclease expression.