Multicellular living organisms and unmodified parts thereof and – Nonhuman animal
Patent
1994-05-19
1997-10-07
Crouch, Deborah
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
424 92, C12N 500, C12P 1500, A61K 4900
Patent
active
056750609
ABSTRACT:
A transgenic animal model for arthritis is disclosed. The arthritic condition results from genetic (or immunologic) manipulations that result in the T cell receptor (TCR) repertoire of the animal being substantially limited relative to the TCR repertoire of a wildtype control animal. The TCR repertoire of the arthritic animal, albeit limited, is functionally viable. In a preferred embodiment, the invention relates to transgenic arthritic mice wherein arthritis results from (1) a transgenic allele which encodes and expresses TCR .alpha. and .beta. subunits that combine in T lymphocytes of the transgenic animal to form a TCR that recognizes an antigen comprising one or more epitopes of an oligopeptide derived from amino acids 41-61 of bovine pancreatic ribonuclease and/or (2) polypeptide arthritogenic self antigens derived from endogenous proteins. The transgenic arthritic mice of the invention provides an animal model which faithfully mimics rheumatoid arthritis and by which human arthritogenic and therapeutic anti-arthritic compositions are evaluated. Also provided herein are therapeutic oligopeptides derived from the variable regions of the TCRs of the transgenes of the invention and/or from the amino acid sequence of proteins comprising endogenous polypeptide arthritogenic antigens.
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Benoist Christophe O.
Kouskoff Valerie
Mathis Diane J.
Centre National de la Recherche Scientifique
Crouch Deborah
E.R. Squibb & Sons, Inc.
Institut National de la Sante et de la Recherche Medicale
Universite Louis Pasteur, Strasbourg 1
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