Inbred miniature swine and uses thereof
AssigneeThe General Hospital Corporation
InventorsDavid H. Sachs, Scott Arn
Life of this patent
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Abstract
The invention provides a swine which is homozygous for a major histocompatibility complex haplotype and at least 60% homozygous at all other genetic loci and such animal is propagatable, and a cell or an organ derived therefrom. The invention also provides a method for providing a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous, as well as a method of inducing tolerance in a recipient mammal of a first species to a graft from a donor mammal of a second species.
Claims35
A swine which is homozygous for a major histocompatibility complex haplotype and at least 60% homozygous at all other genetic loci and such animal is propagatable.
A cell from a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous.
A cell nucleus from a swine cell which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous.
An organ from a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous.
A hematopoietic stem cell preparation from a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous.
A herd of swine which are homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous.
A plurality of swine which are homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous.
A method for providing a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous, comprising:
- providing a first swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ but which is homozygous at less than 60% of all other loci;
- (1) providing a second swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, which is of the same haplotype as the first swine, but which is homozygous at less than 60% of all other loci, which is not a sibling, parent or offspring of the first swine;
- (2) mating said first and second swine to provide an offspring;
- (3) mating said offspring to a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, which is of the same haplotype as the first swine but which is homozygous at less than 60% of all other loci, which is preferably not a sibling, parent or offspring of the offspring;
- (4) repeating step (3) for at least 18 generations;
- (5) performing a brother sister mating from the offspring of the final mating of step (4) to produce at least on male and one female sibling;
- and
- (6) performing brother sister matings form the siblings of step (5) and for at least 5 additional generations,
- thereby providing a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous.
A method of providing a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous, comprising mating a male swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous, with a female swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous,
- thereby providing a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous.
A method of providing a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous, comprising:
- transferring swine genetic material which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ and in which at least 60% of all other genetic loci are homozygous, to a cell, wherein said cell is capable of developing into a swine;
- and allowing said cell to develop into a swine,
- thereby providing a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous.
A method of preparing a transgenic swine, comprising:
- providing a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which all other genetic loci are at least 60% homozygous;
- and
- introducing a transgene into said swine,
- thereby preparing a transgenic swine.
A method of inducing tolerance in a recipient mammal of a first species to a graft from a donor mammal of a second species, comprising:
- providing a donor mammal which is from a herd which is homozygous for a major histocompatibility complex haplotype and at least 60% homozygous at all other genetic loci;
- introducing into the recipient mammal, tolerance inducing tissue;
- providing a graft from the donor mammal or from a second donor mammal from the herd;
- and
- introducing the graft into the recipient,
- thereby inducing tolerance in a recipient mammal of a first species to a graft from a mammal of the second species.
Dependencies are inferred from the claim text.