Transgenic animal model of bone mass modulation

Abstract

The present invention relates to methods and materials used to express the HBM protein in animal cells and transgenic animals. The present invention also relates to transgenic animals expressing the high bone mass gene, the corresponding wild-type gene, and mutants thereof. 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. In preferred embodiments, the present invention is directed to methods for treating, diagnosing and preventing osteoporosis.

1 - 37 . (canceled) 
     
     
         38 . A nucleic acid for gene targeting by homologous recombination comprising a first section homologous to mouse LRP5 gene and a second section homologous to another section of mouse LRP5 gene, and between the first and the second section a middle section comprising an engineered deletion of a portion of the LRP5 gene, a nucleic acid sequence change, or a nucleic acid insertion, and wherein the nucleic acid is capable of homologous recombination with the endogenous gene. 
     
     
         39 . The nucleic acid of  claim 38 , wherein the middle section comprises an engineered deletion of the ATG start codon, an engineered frame-shift mutation, an engineered stop codon, a neomycin resistance sequence, a loxP recombination site, or a synthetic transcriptional pause sequence. 
     
     
         40 . The nucleic acid of  claim 38 , further comprising both intron and exon sequences of the mouse LRP5 gene. 
     
     
         41 . The isolated nucleic acid of  claim 38 , further comprising a codon encoding a glycine to valine change at position 170 of the amino acid sequence of the mouse LRP5 gene. 
     
     
         42 - 44 . (canceled)