Astrocyte-specific transcription of human genes
AssigneeThe United States of America Department of Health and Human Services
InventorsMichael Brenner, Francois Besnard, Yoshihiro Nakatani
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AssigneeThe United States of America Department of Health and Human Services
InventorsMichael Brenner, Francois Besnard, Yoshihiro Nakatani
Estimating the term…
Three unique control DNA sequences of the glial fibrillary acidic (gfa) protein gene have been identified upstream of its basal promoter that are capable of regulating astrocyte-specific transcription of the human gene for glial fibrillary acidic protein (GFAP). One or more of those three regions alone or together with the SV40 early promoter and SV40 enhancer control expression of endogenous or heterologous protein in astrocytes. Transgenic animals expressing amyloid protein can be prepared and used as a model for evaluating Alzheimer's disease. Many heterologous proteins can be expressed in the astrocytes so as to take advantage of the growing list of astrocyte functions. Such proteins include hormones, growth factors, and their receptors. Examples include basic fibroblast growth factor (bFGF), acidic FGF (aFGF), platelet derived growth factor (PDGF), insulin like growth factors 1 and 2 (IGF-1, IGF-2), epidermal growth factor (EGF), transforming growth factors .beta.-1 and .beta.-2 (TGF.beta.1, TGF.beta.2), and S100.beta.; other examples totalled proteins encoded by oncogenes like myc, fos, and erb-a, ion channels, like the calcium channel and the potassium channel, and metabolic enzymes, especially ones involved in processing drugs or neurotransmitters; e.g., glutamine synthetase. Additionally, in each case, a dominant dysfunctional protein, an antisense RNA, or a ribozyme, all of which can inhibit the function or production of the protein, can be expressed in astrocytes.
A recombinant DNA molecule comprising a nucleotide sequence from nucleotide position -2163 to nucleotide position +88 of a human gene encoding glial fibrillary acidic protein, where +1 is the RNA start site, operably linked to a heterologous gene.
A recombinant DNA molecule comprising the following operatively linked elements:
A recombinant DNA molecule comprising the following operatively linked elements ordered 5' to 3':
An isolated human astrocyte-specific DNA expression vector comprising the following elements operably linked in 5' to 3' order:
A recombinant DNA molecule comprising three control regions, wherein two of said control regions have the nucleotide sequence GCCGCNNCCCAG (SEQ ID NO:5) and the third of said control regions has the nucleotide sequence CTGGGNNGCGGC (reverse complement of SEQ ID NO:5), wherein all of said control regions are operatively linked to a basal promoter and a heterologous gene, at a position upstream of said basal promoter, such that the transcription of said heterologous gene is increased compared to the transcription of said heterologous gene in the absence of said nucleotide sequences when said recombinant DNA molecule is expressed in a host cell.
An isolated human astrocyte-specific DNA expression vector comprising the following elements operably linked in 5' to 3' order:
A recombinant DNA molecule comprising the following operatively linked elements:
An isolated human astrocyte-specific DNA expression vector comprising the following elements operably linked in 5' to 3' order:
An isolated human astrocyte-specific DNA expression vector comprising the following elements operably linked in 5' to 3' order:
Dependencies are inferred from the claim text.