HUMAN DIACYLGLYCEROL ACYLTRANSFERASE 2 (DGAT2) FAMILY MEMBERS AND USES THEREFOR

• US 20100035339A1
• Filed: 04/30/2009
• Published: 02/11/2010
• Est. Priority Date: 12/19/2001
• Status: Abandoned Application

• Current Assignee: Brian K. Hubbard, Rosana Kapeller-Libermann, Ruth E. Gimeno, Zhidan Wu
• Original Assignee: Brian K. Hubbard, Rosana Kapeller-Libermann, Ruth E. Gimeno, Zhidan Wu
• Inventors: HUBBARD, Brian K., KAPELLER-LIBERMANN, Rosana, WU, Zhidan, GIMENO, Ruth E.
• Application Number:
  US12/433,304
• Publication Number:
  US 20100035339A1
• Time in Patent Office: Days
• US Class Current: 435/325
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C12N 9/1029 transferring groups other than amino-acyl groups (2.3.1)
• CPC Class Codes: C12Q 1/48 involving transferase
• CPC Class Codes: C12Y 203/0102 Diacylglycerol O-acyltransferase (2.3.1.20)
• CPC Class Codes: G01N 2333/91051 Acyltransferases other than aminoacyltransferases (general) (2.3.1)
• CPC Class Codes: G01N 2800/044 Hyperlipemia or hypolipemia, e.g. dyslipidaemia, obesity
• CPC Class Codes: G01N 33/573 for enzymes or isoenzymes

Abstract

The present invention relates to compositions and methods for the diagnosis and treatment of obesity and related metabolic disorders. The invention provides isolated nucleic acids molecules, designated DGAT2 family member nucleic acid molecules, which encode diacylglycerol acyltransferase family members. The invention also provides recombinant expression vectors containing DGAT2 family member nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a DGAT2 family member gene has been introduced or disrupted. The invention still further provides isolated DGAT2 family member proteins, fusion proteins, antigenic peptides and anti-DGAT2 family member antibodies. Methods of use of the provided DGAT2 family member compositions for screening, diagnostic and therapeutic methods in connection with obesity disorders are also disclosed.

Claims

1. An isolated nucleic acid molecule selected from the group consisting of:

(a) A nucleic acid molecule comprising a nucleotide sequence which is at least 85% identical to the nucleotide sequence of SEQ ID NO;

7, SEQ ID NO;

19, or SEQ ID NO;

61;

(b) A nucleic acid molecule comprising a fragment of at least 300 nucleotides of the nucleotide sequence of SEQ ID NO;

7, SEQ ID NO;

19 or SEQ ID NO;

61;

(c) A nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO;

2, SEQ ID NO;

4, SEQ ID NO;

6, SEQ ID NO;

8, SEQ ID NO;

12, SEQ ID NO;

14, SEQ ID NO;

16, SEQ ID NO;

18, SEQ ID NO;

20 and SEQ ID NO;

62;

(d) A nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO;

8, SEQ ID NO;

20, or SEQ ID NO;

62, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO;

8, SEQ ID NO;

20 or SEQ ID NO;

62;

(e) A nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO;

8, SEQ ID NO;

20 or SEQ ID NO;

62, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising a sequence consisting of SEQ ID NO;

7, SEQ ID NO;

19, or SEQ ID NO;

61 or a compliment thereof, under stringent conditions; and

(f) A nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of SEQ ID NO;

1, SEQ ID NO;

3, SEQ ID NO;

5, SEQ ID NO;

11, SEQ ID NO;

13, SEQ ID NO;

15, SEQ ID NO;

17, SEQ ID NO;

19, and SEQ ID NO;

61.

2. The isolated nucleic acid molecule of claim 1, which is selected from the group consisting of:

(a) A nucleic acid comprising the nucleotide sequence of SEQ ID NO;

7, SEQ ID NO;

19 or SEQ ID NO;

61, and

(b) A nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO;

8, SEQ ID NO;

20 or SEQ ID NO;

62.

3. The nucleic acid molecule of claim 1 further comprising vector nucleic acid sequences or nucleic acid sequences encoding a heterologous polypeptide.

4. A host cell which contains the nucleic acid molecule of claim 1.

5. A non-human mammalian host cell containing the nucleic acid molecule of claim 1.

6. An isolated polypeptide selected from the group consisting of:

(a) A polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 85% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO;

7, SEQ ID NO;

19 or SEQ ID NO;

61, or a compliment thereof;

(b) A naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO;

8, SEQ ID NO;

20 or SEQ ID NO;

62, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO;

7, SEQ ID NO;

19 or SEQ ID NO;

61 or a compliment thereof under stringent conditions;

(c) A fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO;

8, SEQ ID NO;

20 or SEQ ID NO;

62, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO;

8, SEQ ID NO;

20 or SEQ ID NO;

62; and

(d) A polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO;

2, SEQ ID NO;

4, SEQ ID NO;

6, SEQ ID NO;

8, SEQ ID NO;

12, SEQ ID NO;

14, SEQ ID NO;

15, SEQ ID NO;

18, SEQ ID NO;

20 and SEQ ID NO;

62.

7. The polypeptide of claim 6 further comprising heterologous amino acid sequences.

8. An antibody which selectively binds to a polypeptide of claim 6.

9-29. -29. (canceled)