title: Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae.
abstract: We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome-carrying spermatozoa. Notably, these male mosquitoes also induced complete early dominant embryo lethality in crosses with wild-type females. Morphological and molecular data indicated that all spermatozoa, irrespectively of the inheritance of the transgene, carried a substantial amount of I-PpoI protein that could attack the maternally inherited chromosome X of the embryo. Besides the obvious implications for implementing vector control measures, our data demonstrated the feasibility of generating synthetic sex distorters and revealed the intriguing possibility of manipulating maternally inherited genes using wild-type sperm cells carrying engineered endonucleases.
authors.affiliation: Faculty of Life Science, Imperial College London, London, United Kingdom.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Windbichler
authors.forename: Philippos Aris
authors.initials: PA
authors.lastname: Papathanos
authors.forename: Andrea
authors.initials: A
authors.lastname: Crisanti
mesh_terms: D000818:Animals; D000852:Anopheles / Q000196:embryology / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D003433:Crosses, Genetic; D003850:Deoxyribonuclease I / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000201:enzymology / Q000502:physiology; D005260:Female; D018390:Gene Targeting; D005818:Genetic Engineering; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009026:Mortality; D009032:Mosquito Control; D012729:Sex Chromosome Aberrations; D012730:Sex Chromosomes / Q000201:enzymology / Q000235:genetics; D012744:Sex Ratio; D013045:Species Specificity; D013091:Spermatogenesis; D013094:Spermatozoa / Q000201:enzymology / Q000502:physiology
chemical_list: D019476:Insect Proteins; D003850:Deoxyribonuclease I