Compositions and methods for the study and diagnosis of prion diseases
OwnerDavid A. Harris, Richard S. Stewartinventors
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Abstract
The present invention presents novel characteristics of a transmembrane form of PrP (CtmPrP) that is retained in the endoplasmic reticulum, and contains an uncleaved, N-terminal signal peptide as well as a C-terminal glycolipid anchor. The invention also identifies a mutant form of PrP that is synthesized exclusively with the CtmPrP topology as well as related nucleic acid sequences and transfected cells and mammalian animals. Compositions and methods for the further study of CtmPrP and mutant PrP, and their role in the causation and diagnosis of prion related diseases are further embodied in the invention.
Claims41
A method for selective recognition of CtmPrP in a mammal comprising identifying the presence of an uncleaved signal peptide on said CtmPrP.
An antibody that binds specifically to the uncleaved signal peptide region on CtmPrP or an immunogenic fragment of said signal peptide region.
An antibody that binds specifically to the first 22 amino acids of SEQ ID:
- 5.
An antibody that binds specifically to the region of the cleavage site of the uncleaved signal peptide on CtmPrP.
A method of diagnosing prion caused disease in a mammalian patient by identifying the presence of an uncleaved signal peptide on CtmPrP.
A method of diagnosing prion caused diseases in a mammalian patient comprising utilizing components of endoplasmic reticulum stress response pathways as molecular markers.
An isolated nucleic acid comprising a sequence that encodes a polypeptide having the sequence of SEQ ID:
- 8 and conservative amino acid substitutions therein.
An isolated nucleic acid comprising the nucleic acid sequence of SEQ ID:
- 4 or a degenerate variant of SEQ ID:
- 4.
An isolated nucleic acid comprising a sequence that encodes a polypeptide having the sequence of SEQ ID:
- 6 and conservative amino acid substitutions therein.
An isolated nucleic acid comprising the nucleic acid sequence of SEQ ID:
- 2 or a degenerate variant of SEQ ID:
- 2.
An expression vector comprising the nucleic acid of SEQ ID:
- 4 operably linked to an expression control sequence.
An expression vector comprising the nucleic acid of SEQ ID:
- 2 operably linked to an expression control sequence.
A method of expressing CtmPrP in a cell comprising:
- providing an expression vector having SEQ ID:
- 4 or degerate variants thereof, introducing the vector into a cell;
- and
- maintaining the cell under conditions permitting expression of CtmPrP in the cell.
A method of expressing CtmPrP in a cell comprising:
- providing an expression vector having SEQ ID:
- 2 or degerate variants thereof, introducing the vector into a cell;
- and
- maintaining the cell under conditions permitting expression of CtmPrP in the cell.
Dependencies are inferred from the claim text.