The present invention relates to a method of producing an ungulate having
both copies of the IgM heavy chain (mu) rag-1 and/or rag-2 gene
eliminated from its genome. Animals which have IgM, rag-1 and/or rag-2
eliminated from their genome are unable to conduct the gene
rearrangements that are necessary to generate the antigen receptors of B-
or T-lymphocytes, and therefore will not develop native B- or T-cells.
Because they are unable to produce B- and T-lymphocytes, these IgM,
rag-1, or rag-2 ungulates cannot reject human hematopoietic stem cell
preparations, and B- and T-lymphocytes which develop therefrom.
Therefore, the present invention also involves injecting into IgM, rag-1,
and/or rag-2 deficient ungulates, in utero or shortly after birth, human
B- and T-lymphocytes whose immune systems produce human immunoglobulin
that can be processed for therapeutic uses in humans.