Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae.
Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae.
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DOI：
10.1371/journal.pgen.1000291
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发表时间：
2008-12
期刊：
影响因子：
4.5
通讯作者：
Crisanti A
中科院分区：
文献类型：
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作者：
Windbichler N;Papathanos PA;Crisanti A
我们利用归巢核酸内切酶I-PpoI对X连锁冈比亚按蚊28 S核糖体基因的高选择性来选择性靶向携带X染色体的精子。我们的数据表明，在杂合子男性中，I-PpoI在睾丸中的表达诱导了对携带Y染色体的精子的强烈偏好。值得注意的是，这些雄性蚊子也诱导完全的早期显性胚胎与野生型女性的杂交致死。形态学和分子数据表明，所有的精子，不管遗传的转基因，携带大量的I-PpoI蛋白，可以攻击母系遗传的胚胎X染色体。除了实施矢量控制措施的明显影响，我们的数据表明，产生合成的性别扭曲的可行性，并揭示了有趣的可能性操纵母系遗传基因使用野生型精子携带工程核酸内切酶。 A.冈比亚蚊子是人类疟疾的主要传播媒介。现有的控制措施对这些蚊子的不足，促使研究遗传控制的方法。我们通过基因工程改造了A.冈比亚蚊子在精子发育期间表达一种酶，该酶选择性地切割仅存在于位于X染色体上的一个必需基因家族上的DNA序列。我们发现，在杂合雄蚊中，这种遗传修饰在与野生型雌蚊杂交时诱导了完全的早期显性胚胎致死。所有来自这些男性的精子，包括那些不含遗传修饰的精子，都携带着X染色体切割酶，这种酶可以攻击胚胎中母系遗传的X染色体。此外，这种遗传修饰引入了对携带X染色体的精子的强烈的负偏好。这些转基因蚊子满足了实施基于遗传不育的病媒控制措施的一些要求，但我们的数据也表明了产生合成性别扭曲的可行性，并揭示了使用携带酶的野生型精子操纵母系遗传基因的可能性，这些酶旨在攻击选定的母系DNA序列。
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. A. gambiae mosquitoes are the main vectors of human malaria. The inadequacy of existing control measures for these mosquitoes has prompted research into methods for genetic control. We have genetically engineered A. gambiae mosquitoes to express, during spermatozoa development, an enzyme that selectively cuts a DNA sequence present only on a family of essential genes located on the X chromosome. We found that in heterozygous male mosquitoes, this genetic modification induced complete early dominant embryo lethality in crosses with wild-type females. All spermatozoa from these males, including those not containing the genetic modification, carried the chromosome X cutting enzyme that could attack the maternally inherited X chromosome of the embryo. Furthermore, this genetic modification introduced a strong, negative bias toward X chromosome–carrying spermatozoa. These transgenic mosquitoes fulfil a number of requirements for implementing vector control measures based on genetic sterility, but our data also demonstrate the feasibility of generating synthetic sex distorters and reveal the possibility of manipulating maternally inherited genes using wild-type sperm cells carrying enzymes designed to attack selected maternal DNA sequences.
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影响因子：
56.9
作者：
Chen, Chun-Hong;Huang, Haixia;Hay, Bruce A.
通讯作者：
Hay, Bruce A.
影响因子：
2.4
作者：
Horn, C;Wimmer, EA
通讯作者：
Wimmer, EA
影响因子：
5.3
作者：
ELLISON, EL;VOGT, VM
通讯作者：
VOGT, VM
影响因子：
5.6
作者：
Argast, GM;Stephens, KM;Monnat, RJ
通讯作者：
Monnat, RJ
DOI：
10.1007/978-0-387-78225-6_11
发表时间：
2008-01-01
期刊：
TRANSGENESIS AND THE MANAGEMENT OF VECTOR-BORNE DISEASE
影响因子：
--
作者：
Cook, Peter E.;McMeniman, Conor J.;O'Neill, Scott L.
通讯作者：
O'Neill, Scott L.