Nogo receptor homologs
View Patent ↗The invention relates generally to genes that encode proteins that inhibit axonal growth. The invention relates specifically to genes encoding NgR protein homologs in humans and mice. The invention also includes compositions and methods for modulating the expression and activity of Nogo and the NgR proteins. Specifically, the invention includes peptides, proteins and antibodies that block Nogo-mediated inhibition of axonal extension. The compositions and methods of the invention are useful in the treatment of cranial or cerebral trauma, spinal cord injury, stroke or a demyelinating disease.
1. An isolated polynucleotide comprising a first nucleic acid which encodes a polypeptide at least 80% identical to a polypeptide comprising amino acids 1 to 310 of SEQ ID NO:2, wherein said polypeptide decreases inhibition of axonal elongation.
2. The polynucleotide of claim 1 , wherein said polypeptide is at least 90% identical to amino acids 1 to 310 of SEQ ID NO:2.
3. The polynucleotide of claim 2 , wherein said polypeptide is at least 95% identical to amino acids 1 to 310 of SEQ ID NO:2.
4. The polynucleotide of claim 3 wherein said polypeptide comprises amino acids 1 to 310 of SEQ ID NO:2.
5. The polynucleotide of claim 1 , further comprising a second nucleic acid.
6. The polynucleotide of claim 5 , wherein said second nucleic acid encodes a heterologous polypeptide.
7. The polynucleotide of claim 6 , wherein said heterologous polypeptide forms a fusion protein with the polypeptide encoded by said first nucleic acid.
8. The polynucleotide of claim 7 , wherein said heterologous polypeptide is Fc.
9. The polynucleotide of claim 7 , wherein said heterologous polypeptide is selected from the group consisting of Glutathione S-transferase (GST), a Histidine tag (His tag), and alkaline phosphatase (AP).
10. A vector comprising the polynucleotide of claim 1 .
11. The vector of claim 10 , wherein said polynucleotide is operably linked to one or more expression control elements.
12. An isolated host cell comprising the polynucleotide of claim 1 .
13. The host cell of claim 12 , wherein said polynucleotide is operably linked to one or more expression control elements.
14. An isolated polynucleotide comprising a first nucleic acid which encodes a polypeptide at least 80% identical to a polypeptide comprising amino acids 31 to 310 of SEQ ID NO:2, wherein said polypeptide decreases inhibition of axonal elongation.
15. The polynucleotide of claim 14 , wherein said polypeptide is at least 90% identical to amino acids 31 to 310 of SEQ ID NO:2.
16. The polynucleotide of claim 15 , wherein said polypeptide is at least 95% identical to amino acids 31 to 310 of SEQ ID NO:2.
17. The polynucleotide of claim 16 , wherein said polypeptide comprises amino acids 31 to 310 of SEQ ID NO:2.
18. The polynucleotide of claim 14 , further comprising a second nucleic acid.
19. The polynucleotide of claim 18 , wherein said second nucleic acid encodes a heterologous polypeptide.
20. The polynucleotide of claim 19 , wherein said heterologous polypeptide forms a fusion protein with the polypeptide encoded by said first nucleic acid.
21. The polynucleotide of claim 20 , wherein said heterologous polypeptide is Fc.
22. The polynucleotide of claim 20 , wherein said heterologous polypeptide is selected from the group consisting of Glutathione S-transferase (GST), a Histidine tag (His tag), and alkaline phosphatase (AP).
23. A vector comprising the polynucleotide of claim 14 .
24. The vector of claim 23 , wherein said polynucleotide is operably linked to one or more expression control elements.
25. An isolated host cell comprising the polynucleotide of claim 14 .
26. The host cell of claim 25 , wherein said polynucleotide is operably linked to one or more expression control elements.
27. An isolated polynucleotide comprising a first nucleic acid which encodes, except for 1 to 10 conservative amino acid substitutions, a polypeptide selected from the group consisting of amino acids 1–310 of SEQ ID NO:2 and amino acids 31–310 of SEQ ID NO:2; wherein said polypeptide decreases inhibition of axonal elongation.
28. The polynucleotide of claim 27 , further comprising a second nucleic acid.
29. The polynucleotide of claim 28 , wherein said second nucleic acid encodes a heterologous polypeptide.
30. The polynucleotide of claim 29 , wherein said heterologous polypeptide forms a fusion protein with the polypeptide encoded by said first nucleic acid.
31. The polynucleotide of claim 30 , wherein said heterologous polypeptide is Fc.
32. The polynucleotide of claim 30 , wherein said heterologous polypeptide is selected from the group consisting of Glutathione S-transferase (GST), a Histidine tag (His tag), and alkaline phosphatase (AP).
33. A vector comprising the polynucleotide of claim 27 .
34. The vector of claim 33 , wherein said polynucleotide is operably linked to one or more expression control elements.
35. An isolated host cell comprising the polynucleotide of claim 27 .
36. The host cell of claim 35 , wherein said polynucleotide is operably linked to one or more expression control elements.