Porcine reproductive and respiratory syndrome virus resistant animals
The present invention generally relates to genetically modified swine wherein at least one allele of a SIGLEC1 gene has been inactivated and/or at least one allele of a CD163 gene has been inactivated. Genetically modified swine having both alleles of the SIGLEC1 gene and/or both alleles CD163 gene inactivated are resistant to porcine reproductive and respiratory syndrome virus (PRRSV). Methods for producing such transgenic swine are also provided.
1. A genetically modified swine comprising an alteration in a CD 163 gene sequence, wherein the alteration reduces the expression of CD 163, wherein the alteration is in a non-coding sequence of the CD163 gene, and wherein the swine exhibits increased resistance to porcine reproductive and respiratory syndrome virus (PRRSV).
2. The genetically modified swine of claim 1 , wherein the non-coding sequence comprises an intron, a promoter, a 5′-untranslated sequence, or a 3′-untranslated sequence.
3. The genetically modified swine of claim 2 , wherein the non-coding sequence comprises a promoter.
4. The genetically modified swine of claim 1 , wherein the alteration comprises an insertion, a deletion, a point mutation, or a combination of any thereof.
5. The genetically modified swine of claim 1 , wherein the wherein the swine further comprises a mutation in one or both alleles of a SIGLEC1 gene.
6. The genetically modified swine of claim 5 , wherein the mutation comprises a partial deletion, a complete deletion, a frame-shift mutation, a nonsense mutation, a missense mutation, a point mutation, or a combination of any thereof.
7. The genetically modified swine of claim 5 , wherein the SIGLEC1 allele has been mutated by deletion of part of exon 1 and all of exons 2 and 3.
8. The genetically modified swine of claim 1 , wherein the swine does not comprise a mutation in either allele of a SIGLEC1 gene.
9. A genetically modified swine comprising an alteration in a CD 163 gene sequence, wherein the swine exhibits increased resistance to porcine reproductive and respiratory syndrome virus (PRRSV), wherein the alteration reduces the expression of CD163.
10. The genetically modified swine of claim 9 , wherein the alteration in the CD163 gene sequence comprises an alteration in a coding region of the CD163 gene sequence.
11. The genetically modified swine of claim 9 , wherein the alteration in the CD163 gene sequence comprises an alteration in a non-coding region of the CD163 gene sequence.
12. The genetically modified swine of claim 11 , wherein the non-coding sequence comprises an intron, a promoter, a 5′-untranslated sequence, or a 3′-untranslated sequence.
13. The genetically modified swine of claim 12 , wherein the non-coding sequence comprises a promoter.
14. The genetically modified swine of claim 9 , wherein the alteration comprises an insertion, a deletion, a frame shift mutation, a nonsense mutation, a missense mutation, a point mutation, or a combination thereof.
15. The genetically modified swine of claim 9 , wherein the swine further comprises a mutation in one or both alleles of a SIGLEC1 gene.
16. The genetically modified swine of claim 15 , wherein the mutation comprises a partial deletion, a complete deletion, a frame-shift mutation, a nonsense mutation, a missense mutation, a point mutation, or a combination of any thereof.
17. The genetically modified swine of claim 15 , wherein the SIGLEC1 allele has been mutated by deletion of part of exon 1 and all of exons 2 and 3.
18. The genetically modified swine of claim 9 , wherein the swine does not comprise a mutation in either allele of a SIGLEC1 gene.
19. Progeny of the genetically modified swine of claim 9 , wherein the progeny comprise the alteration in the CD163 gene sequence.