Transgenic animal model for degenerative diseases of cartilage
AssigneeWyeth
InventorsLisa Ann Neuhold, Loran Marie Killar
Life of this patent
Estimating the term…
Abstract
The present invention provides animal model systems for cartilage-degenerative disease, which comprise transgenic animals which can express recombinant matrix-degrading enzymes (MDEs), particularly matrix metalloproteinases (MMPs), in a temporally and spatially regulated manner. The invention also provides methods for producing phenotypic indicators of cartilage-degenerative disease in a mammal and methods for determining the potential of a composition to counteract cartilage-degenerative disease. The invention also provides isolated nucleic acids encoding proMMP polypeptides that exhibit constitutive enzymatic activity and isolated proMMP polypeptides.
Claims27
A transgenic non-human mammal or the progeny thereof having somatic and germline cells which contain, in stably integrated form, a recombinant gene encoding a polypeptide comprising an enzymatically active matrix-degrading enzyme, wherein said recombinant gene is selectively expressed in chondrocytes of said mammal and said expression results in pathological symptoms characteristic of cartilage-degenerative disease.
A transgenic animal or the progeny thereof having somatic and germline cells which contain a stably integrated first recombinant gene encoding a polypeptide selected from the group consisting of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16, MMP-17 and enzymatically active variants thereof.
A transgenic mouse or the progeny thereof having somatic and germline cells which contain in stably integrated form:
- (i) a first recombinant gene comprising a sequence encoding a variant MMP-13 polypeptide comprising MMP-13*, wherein said sequence is operably linked to a tetO7 promoter;
- and
- (ii) a second recombinant gene encoding a tTA protein operatively linked to sequences derived from a type II collagen promoter.
An isolated nucleic acid encoding enzymatically active proMMP-13, wherein said nucleic acid has a sequence selected from the group consisting of the sequence depicted in SEQ ID NO:
- 1, sequence-conservative mutants thereof, and function-conservative mutants thereof.
Dependencies are inferred from the claim text.