Human tyrosine hydroxylase promoter and uses thereof
The present invention provides an isolated, purified and characterized human tyrosine hydroxylase (hTH) promoter nucleic acid sequence. The invention further provides a method of selecting TH positive (TH+) cells by preparing a construct comprising a hTH promoter operably linked to a heterologous nucleic acid sequence, for example, green fluorescent protein encoding sequence, and transfecting cells, particularly stem cells, with the construct. The invention also provides a hTH promoter, useful in gene therapeutic applications in driving therapeutic genes or other nucleic acid sequences operably linked to the hTH promoter. Additionally, the invention provides cell lines and transgenic animals expressing a transgene comprising the hTH promoter operably linked to a heterologous sequence, which cell lines and transgenic animals are useful for isolating TH+ cells for transplantation or for screening of therapeutic agents that affect TH+ function. Methods of producing cell lines and transgenic animals also provided.
1. The isolated human tyrosine hydroxylase promoter nucleic acid sequence of SEQ ID NO:1.
2. A nucleic acid construct comprising a human tyrosine hydroxylase promoter sequence of SEQ ID NO: 1 operably linked to a heterologous nucleic acid sequence.
3. The construct of claim 2 , wherein the heterologous nucleic acid sequence encodes a reporter molecule.
4. The construct of claim 3 , wherein the reporter molecule is a fluorescent protein.
5. The construct of claim 2 , wherein the heterologous nucleic acid sequence encodes a protein.
6. The construct of claim 5 , wherein the protein is selected from the group consisting of a glial cell derived neurotrophic factor, superoxide dismutase, fibroblast growth factor, and brain derived neurotrophic factor.