Astrocyte-specific transcription of human genes

Details Astrocyte-specific transcription of human genes Astrocyte-specific transcription of human genes

1994-02-16

1997-05-06

Walsh, Stephen G.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

435 697, 4353201, 435368, 435354, 435325, 536 234, 536 235, 536 241, C12N 1585, C12N 1562, C12N 1510

Patent

active

056270470

ABSTRACT:
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.

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