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. Papathanos, Nikolai Windbichler, Miriam Menichelli, Austin Burt, Andrea Crisanti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

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.

Original languageAmerican English
Article number65
JournalBMC Molecular Biology
Volume10
DOIs
StatePublished - 2 Jul 2009
Externally publishedYes

Bibliographical note

Funding Information:
We would like to thank Kalle Magnusson and Tony Nolan for experimental help and for proofreading the manuscript. We would also like to thank Janet Meredith for her data on the Anopheles gambiae vasa transcripts, which have been deposited into Genbank (Vasa 5' RACE accession number EU522080 and 3' RACE accession numbers EU522081 and EU522082). Funded by a Grant from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative. Funded by a Grant of the BBSRC.

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