Gene encoding MNR2 and uses thereof

• US 6,387,656 B1
• Filed: 09/29/1998
• Issued: 05/14/2002
• Est. Priority Date: 09/29/1998
• Status: Expired due to Fees

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: William, Christopher, Tanabe, Yasuto, Jessell, Thomas M.
• Primary Examiner(s): Ketter, James
• Assistant Examiner(s): SCHNIZER, RICHARD A
• Application Number:
  US09/162,524
• Time in Patent Office: 1,323 Days
• Field of Search: 536/23.1, 536/23.5, 435/320.1, 435/69.1, 435/252.3, 435/325
• US Class Current: 435/69.1
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: C07K 14/47 from mammals

Abstract

This invention provides an isolated nucleic acid molecule encoding a motor neuron restricted pattern, MNR2, protein. This invention provides an isolated nucleic acid molecule of at least 15 contiguous nucleotides capable of specifically hybridizing with a unique sequence included within the sequence of the nucleic acid molecule encoding a MNR2 protein. This invention provides a purified MNR2 protein, a polyclonal and monoclonal antibody directed to an epitope of an MNR2 protein. This invention provides a method of inducing differentiation somatic motor neurons which comprises expressing MNR2 protein in any neural progenitor cells. This invention provides a transgenic animal which expresses an MNR2 protein. This invention provides a pharmaceutical composition comprising a MNR2 protein and pharmaceutically acceptable carrier. This invention provides methods of treating subjects afflicted with an abnormality associated with a lack of normally functioning motor neurons, neurodegenerative disease, an acute nervous system injury and a neuromuscular disease which comprises contacting the subject with a pharmaceutical composition comprising a MNR2 protein and pharmaceutically acceptable carrier. This invention provides a functionally equivalent analog of MNR2 that induces or prevents MNR2 differentiation of neural progenitor cells.

Claims

1. An isolated nucleic acid which encodes a homebox motor neuron restricted pattern polypeptide designated MNR2 having the amino acid sequence set forth in SEQ ID NO:

1.

2. The isolated nucleic acid of claim 1, wherein the isolated nucleic acid is DNA.

3. The isolated nucleic acid of claim 2, wherein the isolated nucleic acid is cDNA.

4. The isolated nucleic acid of claim 1, wherein the isolated nucleic acid is RNA.

5. The isolated nucleic acid of claim 1 operatively linked to a promoter of RNA transcription.

6. A vector which comprises the isolated nucleic acid of claim 1, operatively linked to a promoter of RNA transcription.

7. The vector of claim 6, wherein the vector is a plasmid.

8. The vector of claim 7, wherein the plasmid is designated pcs2+cMNR2.3 (ATCC Accession No. 203294).

9. The isolated nucleic acid of claim 3, wherein the isolated nucleic acid comprises nucleotides having the sequence set forth in SEQ ID NO:

2.

10. A host vector system which comprises the vector of claim 6 and a suitable host cell.

11. The host vector system of claim 10, wherein the host cell is selected from the group consisting of a bacterial cell, a plant cell, an insect cell, and a mammalian cell.

12. A method of producing a polypeptide having the biological activity of a homeobox motor neuron restricted pattern polypeptide designated MNR2 which comprises growing the host vector system of claim 10 under suitable conditions permitting production of the polypeptide and recovering the polypeptide so produced.

13. An isolated nucleic acid having a nucleic acid sequence which is complementary to the entire sequence of the nucleic acid of claim 1.

14. The isolated nucleic acid of claim 13, wherein the isolated nucleic acid is DNA.

15. The isolated nucleic acid of claim 13, wherein the isolated nucleic acid is RNA.

16. A method of producing a purified homeobox motor neuron restricted pattern polypeptide designated MNR2 which comprises:

a) inserting the nucleic acid of claim 1 into a suitable vector;

b) introducing the resulting vector into a suitable host cell;

c) selecting for a cell which expresses homeobox motor neuron restricted pattern polypeptide designated MNR2;

d) culturing the selected cell so as to produce the homeobox motor neuron restricted pattern polypeptide designated MNR2; and

e) recovering the homeobox motor neuron restricted pattern polypeptide designated MNR2 produced.