Inbred miniature swine and uses thereof

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.

1 .- 23 . (canceled)  
   
   
       24 . 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.  
   
   
       25 . The method of  claim 24 , wherein said transgene encodes a human growth factor receptor.  
   
   
       26 . The method of  claim 24 , wherein said transgene encodes a cytokine receptor.  
   
   
       27 . 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.  
   
   
       28 . The method of  claim 27 , 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; pl introducing into the recipient mammal, hematopoietic stem cells from said donor mammal; providing a graft from said donor mammal or from said herd; and introducing said graft into said recipient, thereby inducing tolerance in a recipient mammal of a first species to a graft from a donor mammal of a second species.  
   
   
       29 . The method of  claim 27 , wherein said recipient is a primate and said donor is a swine.  
   
   
       30 . The method of  claim 27 , wherein said recipient is a primate and said donor is a miniature swine.  
   
   
       31 . The method of  claim 27 , wherein said recipient is a human and said donor is a swine.  
   
   
       32 . The method of  claim 27 , wherein said recipient is a human and said donor is a miniature swine.  
   
   
       33 . The method of  claim 29 , wherein said swine 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.  
   
   
       34 . The method of  claim 27 , 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, thymic tissue from said donor mammal; providing a graft from said donor mammal, or from said herd; and introducing said graft into said recipient, thereby inducing tolerance in a recipient mammal of a first species to a graft from a donor mammal of the second species.  
   
   
       35 . The method of  claim 27 , comprising: inserting a nucleic acid encoding an MHC antigen into a hematopoietic stem cell of the recipient, wherein the nucleic acid encodes an MHL antigen of a swine from a herd which is homozygous for a major histocompatibility complex haplotype and at least 60% homozygous at all other genetic loci; allowing the MHC antigen encoding nucleic acid to be expressed in the recipient; and preferably, implanting graft in the recipient, wherein the graft is from an animal from the herd.