Patent ID: 8772571
Filing Date: 2014-07-08
Classification: A01K,A61K,A61P,C07K,C12N

Abstract:
1. A method of identifying an agent that modulates bone growth, maintenance and repair, the method comprising: harvesting at least one hematopoietic stem cell; transducing and expressing in the at least one mouse hematopoietic stem cell at least one heterologous nucleic acid comprising a polynucleotide sequence that encodes an osteogenic growth factor comprising a secretable analog of human fibroblast growth factor-2 (FGF-2) encoded by a nucleic acid sequence comprising in a 5′ to 3′ direction: a polynucleotide sequence that encodes a bone morphogenetic protein 2/4 (BMP2/4) hybrid secretion signal peptide sequence and a polynucleotide sequence that encodes a mature human FGF-2 polypeptide comprising a mutation that results in the substitution of an alanine for a cysteine in amino acid position 70 of FGF-2 and a mutation that results in the substitution of an asparagine for a cysteine in amino acid position 88 of FGF-2; introducing the at least one hematopoietic stem cell or a progeny thereof into an immunologically compatible mouse, wherein expression of the secretable analog of human FGF-2 produces an increase in serum level of FGF-2 as compared to immunologically compatible mice engrafted with hematopoietic stem cells transduced with the BMP2/4 hybrid secretion signal peptide sequence and a wild type FGF-2-control; administering an agent to the mouse; and screening for modulation of FGF-2 secretion, wherein an increase in FGF-2 secretion identifies an agent that increases bone growth.