Gridlock nucleic acid molecules, polypeptides, and diagnostic and therapeutic methods
The invention provides a novel gene, gridlock, and its encoded protein. gridlock plays a role in vascular development and modeling, and a mutation in gridlock has been associated with an aortic arch disease, coarctation. Thus, gridlock nucleic acid molecules and polypeptides can be used in methods of diagnosing, treating, and preventing gridlock-related diseases and conditions, such as aortic arch diseases.
1. An isolated nucleic acid molecule comprising a sequence encoding a gridlock polypeptide that comprises (i) a basic domain, (ii) a helix-loop-helix domain, (iii) an Orange domain, and (iv) a protein-protein interaction domain that comprises a YRPW motif, wherein the amino acid sequence of said polypeptide is at least 55% identical to the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4.
2. The nucleic acid molecule of claim 1 , wherein said nucleic acid molecule encodes a human gridlock polypeptide.
3. The nucleic acid molecule of claim 1 , wherein said nucleic acid molecule encodes a polypeptide comprising an amino sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4.
4. The nucleic acid molecule of claim 3 , wherein said nucleic acid molecule encodes a polypeptide comprising an amino acid sequence that is at least 75% identical to the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4.
5. The nucleic acid molecule of claim 1 , wherein said nucleic acid molecule comprises a nucleotide sequence that is at least 51% identical to the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3.
6. The nucleic acid molecule of claim 1 , wherein said nucleic acid molecule is DNA.
7. A vector comprising the nucleic acid molecule of claim 1 .
8. The vector of claim 7 , wherein said vector is an in vitro or ex vivo gene therapy vector.
9. A cell comprising the vector of claim 7 .
10. The nucleic acid molecule of claim 4 , wherein said nucleic acid molecule encodes a polypeptide comprising an amino sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4.
11. The nucleic acid molecule of claim 10 , wherein said nucleic acid molecule encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4.
12. The nucleic acid molecule of claim 5 , wherein said nucleic acid molecule comprises a nucleotide sequence that is at least 60% identical to the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3.
13. The nucleic acid molecule of claim 12 , wherein said nucleic acid molecule comprises a nucleotide sequence that is at least 75% identical to the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3.
14. The nucleic acid molecule of claim 13 , wherein said nucleic acid molecule comprises a nucleotide sequence that is at least 85% identical to the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3.
15. The nucleic acid molecule of claim 14 , wherein said nucleic acid molecule comprises a nucleotide sequence that is at least 90% identical to the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3.
16. The nucleic acid molecule of claim 15 , wherein said nucleic acid molecule comprises a nucleotide sequence that is at least 95% identical to the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3.
17. The nucleic acid molecule of claim 16 , wherein said nucleic acid molecule comprises the sequence of SEQ ID NO:1 or SEQ ID NO:3.