Infertility resulting from transgenic I-PpoI male Anopheles gambiae in large cage trials

Abstract

Objectives: Anopheles gambiae is the primary vector of malaria in sub-Saharan Africa and is a potential target of genetic control programs. We determined the capacity of male A. gambiae created by germline transformation to introduce infertility into stable age-distribution populations. We also determined effects of the transgenes on life history.

Methods: Stable age-distribution populations of A. gambiae mosquitoes were established in large indoor cages. Male mosquitoes carrying an I-PpoI homing endonuclease gene were introduced at ×5 and ×10 release rates where they competed with target male mosquitoes for matings. Similar trials were conducted in small cages with an additional ×1 release level.

Results: Infertility was successfully introduced into all target populations. In supporting experiments, complete female infertility was observed in all strains and species of the A. gambiae complex to which transgenic males were mated. Life history experiments demonstrated that reductions in I-PpoI male vigor exist in the form of reduced adult male emergence, longevity and competitiveness.

Discussion: A. gambiae I-PpoI males are capable of introducing high levels of infertility in target populations in indoor cage trials. This was accomplished despite losses of vigor resulting from the HEG transgene. These results motivate further trials of sexually I-PpoI A. gambiae in outdoor cage and field trials.

Keywords:

• GMO animals
• Reproductive infertility
• Biological pest control
• Insect vectors
• Malaria

We appreciate the use of the environmental chambers and insectaries of the Centers for Disease Control and Prevention. The tuna meal was provided by Jeremie Gilles (International Atomic Energy Agency, Vienna, Austria). The MR4 continues to be an essential source of support which provided many mosquito strains for these studies. This work is funded by a grant from the Foundation for the National Institutes of Health through the Vector-Based Control of Transmission: Discovery Research (VCTR) program of the Grand Challenges in Global Health initiative to AB.