Leucine aminopeptidase1 controls egg deposition and hatchability in male Aedes aegypti mosquitoes.

Sun, Xiaomei; Wang, Xueli; Shi, Kai; Lyu, Xiangyang; Sun, Jian; Raikhel, Alexander S; Zou, Zhen · Nat Commun · 2024

basic_science · Level V

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Abstract

Aedes aegypti are vectors for several arboviruses infecting hundreds of millions of people annually. Controlling mosquito populations by regulating their reproduction is a potential strategy to minimize viral transmission in the absence of effective antiviral therapies or vaccines. Here, we demonstrate that leucine aminopeptidase1 (LAP1), detected by a SWATH-MS-based proteomic screen of female spermathecae, is a crucial determinant in mosquito population expansion. Mitochondrial defects and aberrant autophagy of sperm in LAP1 mutant males (LAP1<sup>-/-</sup>), prepared using CRISPR/Cas9 system, result in a reduction of reproduction in wild-type females that mated with them. The fitness of LAP1<sup>-/-</sup> males is strong enough to efficiently transmit genetic changes to mosquito populations through a low number of hatchable offspring. Thus, LAP1<sup>-/-</sup> males represent an opportunity to suppress mosquito populations and further studies should be undertaken to characterize LAP1's suitability for gene drive usage.

Medical subject headings