HBM variants that modulate bone mass and lipid levels

a technology of lipid levels and variants, applied in the field of genetics, genomics and molecular biology, can solve the problems of increasing the risk of aging, and reducing the effect of bone resorption and formation

a technology of lipid levels and variants, applied in the field of genetics, genomics and molecular biology, can solve the problems of increasing the risk of aging, and reducing the effect of bone resorption and formation

US20090136507A1Inactive Publication Date: 2009-05-28GENOME THERAPEUTICS +1

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  • HBM variants that modulate bone mass and lipid levels
  • HBM variants that modulate bone mass and lipid levels
  • HBM variants that modulate bone mass and lipid levels

Examples

Experimental program
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Effect test

example 1

[0718]The propositus was referred by her physicians to the Creighton Osteoporosis Center for evaluation of what appeared to be unusually dense bones. She was 18 years old and came to medical attention two years previous because of back pain, which was precipitated by an auto accident in which the car in which she was riding as a passenger was struck from behind. Her only injury was soft tissue injury to her lower back that was manifested by pain and muscle tenderness. There was no evidence of fracture or subluxation on radiographs. The pain lasted for two years, although she was able to attend school full time. By the time she was seen in the Center, the pain was nearly resolved and she was back to her usual activities as a high school student. Physical exam revealed a normal healthy young woman standing 66 inches and weighing 128 pounds. Radiographs of the entire skeleton revealed dense looking bones with thick cortices. All bones of the skeleton were involved. Most importantly, th...

example 2

[0720]The present invention describes DNA sequences derived from two BAC clones from the HBM gene region, as evident in Table 7 below, which is an assembly of these clones. Clone b200e21-h (ATCC No. 980812; SEQ ID NOS: 10-11) was deposited at the American Type Culture Collection (ATCC), 10801 University Blvd., Manassas, Va. 20110-2209 U.S.A., on Dec. 30, 1997. Clone b527d12-h (ATCC No. 980720; SEQ ID NOS: 5-9) was deposited at the American Type Culture Collection (ATCC), 10801 University Blvd:, Manassas, Va. 20110-2209 U.S.A., on Oct. 2, 1998. These sequences are unique reagents that can be used by one skilled in the art to identify DNA probes for the Zmax1 gene, PCR primers to amplify the gene, nucleotide polymorphisms in the Zmax1 gene, or regulatory elements of the Zmax1 gene.

example 3

Yeast-2 Hybrid Screen for Peptide Aptamer Sequences to Dkk-1

[0721]Peptide aptamer library construction. A peptide aptamer library, Tpep, was constructed, which provides a means to identify chimeric proteins that bind to a protein target (or bait) of interest using classic yeast two hybrid (Y2H) assays. The Tpep library is a combinatorial aptamer library composed of constrained random peptides, expressed within the context of the disulfide loop of E. coli thioredoxin (trxA), and as C-termini fusion to the S. cerevisiae Gal4 activation domain. The Tpep library was generated using a restriction enzyme modified recombinant Y2H prey vector, pPC86 (Gibco), which contains the trxA scaffold protein.

[0722]Generation of aptamer-encoding sequences. Aptamer-encoding sequences were produced as follows. DNA encoding random stretches of approximately sixteen amino acids surrounded by appropriate restriction sites were generated by semi-random oligonucleotide synthesis. The synthetic oligonucleotid...

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Abstract

The present invention relates to methods and materials used to express an HBM-like polypeptide derived from HBM, LRP5 or LRP6 in animal cells and transgenic animals. The present invention also relates to transgenic animals expressing the HBM-like polypeptides. The invention provides nucleic acids, including coding sequences, oligonucleotide primers and probes, proteins, cloning vectors, expression vectors, transformed hosts, methods of developing pharmaceutical compositions, methods of identifying molecules involved in bone development, and methods of diagnosing and treating diseases involved in bone development and lipid modulation. In preferred embodiments, the present invention is directed to methods for treating, diagnosing and preventing osteoporosis.

Description

FIELD OF THE INVENTION[0001]The present invention relates generally to the field of genetics, genomics and molecular biology. The invention relates to methods and materials used to isolate, detect and sequence a high bone mass gene and corresponding wild-type gene, and mutants thereof. The present invention also relates to the high bone mass (HBM) gene, the corresponding wild-type gene, and mutants thereof. The genes identified in the present invention are implicated in the ontology and physiology of bone development. The invention also provides nucleic acids, proteins, cloning vectors, expression vectors, transformed hosts, methods of developing pharmaceutical compositions, methods of identifying molecules involved in bbne development, and methods of diagnosing and treating diseases involved in bone development and lipid levels. The invention further relates to transgenic animals for studying the HBM phenotype and related variant phenotypes, the mechanism of action of the HBM gene ...

Claims

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Application Information

Patent Timeline
28 May 2009
Publication
US20090136507A1
IPC
A61K39/395; C07K16/18; A01K67/027; A61K35/00; A61K38/00; A61K45/00; A61P3/00; A61P19/00; A61P19/10; C07K14/47; C07K14/51; C12N5/10; C12N15/09; C12N15/12; C12N15/85; C12P21/08; C12Q1/02; C12Q1/68; G01N33/15; G01N33/50; G01N33/53; G01N33/566
CPC
A01K67/0276; G01N2500/00; A01K2207/15; A01K2217/00; A01K2217/05; A01K2217/075; A01K2227/105; A01K2227/50
Inventors
ALLEN, KRISTINA; ANISOWICZ, ANTHONY