Control of growth and repair of gastro-intestinal tissues by gastrokines and inhibitors
AssigneeThe University of Chicago
InventorsTerence Martin, F. Gary Toback, Margaret Walsh-Reitz
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Abstract
A novel group of gastrokines called Gastric Antrum Mucosal Protein is characterized. A member of the group is designated AMP-18. AMP-18 genomic DNA, cDNA and the AMP-18 protein are sequenced for human, mouse and pig. The AMP-18 protein and active peptides derived from it are cellular growth factors. Surprisingly, peptides capable of inhibiting the effects of the complete protein, are also derived from the AMP-18 protein. Cytoprotection and control of mammalian gastro-intestinal tissue growth and repair (restitution) is facilitated by the use of the proteins, making the proteins candidates for therapies in inflammatory bowel disease and gastric ulcers.
Claims12
1-17. (canceled)
An inhibitor of a protein, the protein selected from a group of isolated homologous cellular growth stimulating proteins designated gastrokines, because the proteins are produced by gastric epithelial cells, the protein comprising a consensus amino acid sequence selected from the group consisting of VKE(K/Q)KXXGKGPGG(P/A)PPK(SEQ ID NO:
- 10), VKE(K/Q)KLQGKGPGG(P/A)PPK(SEQ ID NO:
- 25) and VKE(K/Q)KGKGPGG(P/A)PPK(SEQ ID NO:
- 26), and the inhibitor is selected from the group of peptides having an amino acid sequence consisting of KKTCIVHKMKK(SEQ ID NO:
- 14) and KKEVMPSIQSLDALVKEKK(SEQ ID NO:
- 15).
An isolated cDNA molecule encoding a human protein, the protein having the amino acid sequence as shown in FIG. 2.
An isolated DNA molecule comprising the genomic sequence found in DNA derived from a mouse, the genomic sequence shown in FIG. 4.
A mouse with a targeted deletion in a nucleotide sequence in the mouse genome that when expressed without the deletion encodes a protein of the group of gastrokine proteins comprising a consensus amino acid sequence selected from the group consisting of VKE(K/Q)KXXGKGPGG(P/A)PPK(SEQ ID NO:
- 10), VKE(K/Q)KLQGKGPGG(P/A)PPK(SEQ ID NO:
- 25) and VKE(K/Q)KGKGPGG(P/A)PPK(SEQ ID NO:
- 26).
Dependencies are inferred from the claim text.