Randall A Johnson

US Patent:

58593071, Jan 12, 1999

Filed:

Jun 7, 1994

Appl. No.:

8/254989

Inventors:

Peter Mombaerts - Cambridge MA
Susumu Tonegawa - Newton MA
Randall S. Johnson - Boston MA
Virginia Papaioannou - Lexington MA

Assignee:

Massachusetts Institute of Technology - Cambridge MA
Dana Farber Cancer Institute & Tufts University - Boston MA

International Classification:

A61K 4900
G01N 3100
C12N 506
C12N 1506

US Classification:

800 2

Abstract:

Immunodeficient animals are generated by introducing a mutation in RAG-1 into the germline of the animals via gene targeting in embryonic stem cells. The production of mutant RAG-1 deficient mice is detailed. RAG-1 deficient mice have no mature B and T lymphocytes. The arrest of B and T cell differentiation occurs at an early stage and correlates with the inability to perform V(D)J recombination. To date, these mice do not have mature B and T lymphocytes, nor do they express immunoglobulin or T cell receptors. The same strategy can be applied to the generation of other RAG-1 deficient animals, such as rabbits, rats, and pigs, using known techniques. These animals are all useful for the same general purposes as the scid mice, for example, cultivation of human lymphocytes for expression of human immunoglobulin. Other uses include the establishment of continuous lymphoid cell lines and, by crossbreeding with other lines of animals, the establishment of animals developing tumors for use in studying tumor cell developments and treatments.