Mammalian sex selection using genetic modification
First Claim
1. A method for sex selection comprising, introducing a post-meiotically expressed sex selection gene into one of either a Y or X chromosome of a male non-human animal, and propagating said animal.
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Abstract
A method of sex selection in non-human animals is disclosed which comprises transgenic manipulation of the male to modify, destroy or identify gametes having one of either the X or Y chromosome. A chimeric construct comprising a post-meiotic regulatory region in operative association with a sex selection gene is targeted to one of either a Y or X chromosome in the genome of a male animal. The post-meiotic regulatory region may be transition protein 1 promoter. The selection sequence may be a direct or indirect mediator, or a detectable marker. An example of a direct mediator is the Rnase, Barnase. An example of an indirect mediator is the herpes simplex virus thymidine kinase gene, which forms a toxic metabolite in the presence of gancyclovir. Alternatively, a transcriptional activator protein may be linked to the post-meiotic regulatory element and the direct or indirect mediator may be linked to a promoter having a binding site specific for the transcriptional activator. According to the invention a non-human animal is formed which is capable of producing either exclusively male or exclusively female offspring, or a non-human animal is obtained from which X or Y containing gametes may be easily sorted and isolated. The invention is useful in applications which would benefit from the ability to obtain animals of a desired sex.
51 Citations
45 Claims
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1. A method for sex selection comprising, introducing a post-meiotically expressed sex selection gene into one of either a Y or X chromosome of a male non-human animal, and propagating said animal.
- 2. A method for sex selection comprising, introducing in a male animal at least one chimeric construct comprising a regulatory region that is active post-meiotically and in operative association with a sex selection gene, wherein said regulatory region, said sex selection gene, or both said regulatory region and said sex selection gene are bound by nucleotide sequences that target said chimeric construct to one of either a Y or X chromosome and propagating said non-human animal.
- 23. A chimeric construct comprising a post-meiotically active regulatory region in operative association with a sex selection gene, both of said regulatory region and said sex selection gene bound by nucleotide sequences that target said chimeric construct to one of either a Y or X chromosome.
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28. A pair of chimeric constructs comprising a first and a second chimeric construct, said first chimeric construct comprising:
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a first regulatory region in operative association with a gene of interest encoding a regulatory protein, said second construct comprising;
a second regulatory region and an inducible regulatory element capable of regulating the activity of said regulatory region in the presence of said regulatory protein, in operative association with a sex selection gene, wherein said first, said second, or both said first and said second chimeric constructs are bound by nucleotide sequences that target said first, said second, or independently both said first and said second construct, to one of either a Y or X chromosome; and
wherein said first, said second, or both said first and said second regulatory region is a post-meiotically active regulatory region - View Dependent Claims (29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40)
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44. A method of introducing a direct mediator into a host organism comprising, introducing at least one chimeric construct comprising:
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i) an inducible, temporal, or cell specific regulatory region in operative association with a direct mediator; and
ii) an additional regulatory region exhibiting minimal activity and in operative association with an inhibitor, said inhibitor being specific for said direct mediator, and propagating said host animal. - View Dependent Claims (45)
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Specification