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Transgenic non-human animals capable of producing heterologous antibodies of various isotypes

  • US 5,569,825 A
  • Filed: 12/17/1991
  • Issued: 10/29/1996
  • Est. Priority Date: 08/29/1990
  • Status: Expired due to Term
First Claim
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1. A transgenic mouse having a genome comprising a germline copy of an unrearranged human heavy chain immunoglobulin minilocus transgene comprising a plurality of human VH gene segments, a plurality of human D gene segments, a plurality of human JH gene segments, an immunoglobulin heavy chain enhancer, a mu constant region comprised of a mu switch region located upstream from a mu constant gene segment, a gamma constant region comprised of a gamma switch region located upstream from a human gamma constant gene segment, and wherein B lymphocytes of said transgenic mouse rearrange said unrearranged human heavy chain transgene by V-D-J joining to produce a V-D-J gene joined in-frame encoding a heavy chain variable region expressed in polypeptide linkage to the constant region encoded by said human gamma constant gene segment on said transgene by intratransgene isotype switching, and wherein said minilocus transgene has at least one discontinuity of at least 2 kb between said mu and gamma gene segments as compared to a human germline heavy chain locus, wherein said mouse expresses human IgM heavy chains, and as a result of isotype switching, human IgG heavy chains.

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