Methods for Diagnosing and Treating Heart Disease

• US 20090077681A1
• Filed: 05/06/2008
• Published: 03/19/2009
• Est. Priority Date: 02/07/2001
• Status: Abandoned Application

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Fishman, Mark C., Mably, John
• Application Number:
  US12/115,986
• Publication Number:
  US 20090077681A1
• Time in Patent Office: Days
• US Class Current: 800/20
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/00 Genetically modified animals
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2227/40 Fish
• CPC Class Codes: A01K 2267/03 Animal model, e.g. for test or diseases
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: C07K 14/461 from fish
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: G01N 33/5088 of vertebrates

Abstract

The invention provides methods of diagnosing heart disease, such as heart failure, methods for identifying compounds that can be used to treat or to prevent heart disease, and methods of using these compounds to treat or to prevent heart disease. Also provided in the invention are animal model systems that can be used in screening methods.

Claims

1. A method of determining whether a test subject has, or is at risk of developing, a disease or condition related to a heart of glass protein, said method comprising analyzing a nucleic acid molecule of a sample from the test subject to determine whether the test subject has a mutation in a gene encoding said protein, wherein the presence of a mutation indicates that said test subject has, or is at risk of developing, a disease related to a heart of glass protein.

2. The method of claim 1, further comprising the step of using nucleic acid molecule primers specific for a gene encoding a heart of glass protein for nucleic acid molecule amplification of the gene by the polymerase chain reaction.

3. The method of claim 1, wherein determination of whether said gene comprises a mutation is carried out by sequencing a nucleic acid molecule encoding a heart of glass protein from said test subject.

4. The method of claim 1, wherein said test subject is a mammal.

5. The method of claim 1, wherein said test subject is a human.

6. The method of claim 1, wherein said disease or condition is heart disease.

7. The method of claim 1, wherein said disease or condition is heart failure.

8-17. -17. (canceled)

18. A substantially pure zebrafish heart of glass polypeptide.

19. The polypeptide of claim 18, wherein said polypeptide comprises an amino acid sequence that is substantially identical to the amino acid sequence of SEQ ID NO:

2 or SEQ ID NO;

3.

20. The polypeptide of claim 19, wherein said polypeptide comprises the amino acid sequence of SEQ ID NO:

2 or SEQ ID NO;

3.

21. A substantially pure nucleic acid molecule comprising a sequence encoding a zebrafish heart of glass polypeptide of claim 18.

22. The nucleic acid molecule of claim 21, wherein said nucleic acid molecule encodes a polypeptide comprising an amino sequence that is substantially identical to the amino acid sequence of SEQ ID NO:

2 or SEQ ID NO;

3.

23. The nucleic acid molecule of claim 21, wherein said nucleic acid molecule encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:

2 or SEQ ID NO;

3.

24. The nucleic acid molecule of claim 21, wherein said nucleic acid molecules is DNA.

25. A vector comprising the nucleic acid molecule of claim 21.

26. A cell comprising the vector of claim 25.

27. A non-human transgenic animal comprising the nucleic acid molecule of claim 21.

28. The non-human transgenic animal of claim 27, wherein said animal is a zebrafish.

30. A cell from the non-human knockout animal of claim 27.

29. (canceled)

31-33. -33. (canceled)

34. An antibody that specifically binds to a heart of glass polypeptide.

35-36. -36. (canceled)