Transgenic animal assay system for anti-cholinesterase substances

DETAILED DESCRIPTION The present invention provides a transgenic animal assay system which provides a model system for testing for, and treatment of, cholinergic deficits and imbalances in mammals such as cognitive functioning in Alzheimer's patients, certain types of retinal photoreceptor degeneration, hematopoietic disorders, and screening for and susceptibility to anti-cholinesterase compounds.
The present invention provides a recombinant expression vector comprising a DNA sequence encoding a heterologous cholinesterase (ChE) enzyme and promoter.
The heterologous cholinesterase (ChE) enzyme can be normal human AChE; normal human BChE; naturally-occurring variants of the AChE and BChE; synthetic variants of the AChE and PChE, the synthetic variants selected from recombinantly-produced point-mutated and deletion, of one or more residues, mutations; and normal insect ChEs.
For human AChE or biologically active derivatives thereof the ACHE gene can be a DNA sequence which has all or part of the nucleotide sequence substantially as depicted in SEQ ID NO:1, and which encodes an amino acid sequence substantially similar or identical to all or part of the sequence of amino acid residues depicted in SEQ ID NO:2; a DNA sequence which has all or part of the nucleotide sequences substantially as depicted in SEQ ID NO:3, and which encodes an amino acid sequence substantially similar or identical to all or part of the sequence of amino acid residues set forth in SEQ ID NO:4; or a DNA sequence which has all or part of the nucleotide sequence substantially as depicted in SEQ ID NO:5, and which encodes an amino acid sequence substantially similar or identical to all or part of the sequence of amino acid residues set forth in SEQ ID NO:6.
The promoter controlling the transcription of the sequence encoding ChE is a eukaryotic host cell compatible promoter such as CMV, CMV-like, ACHE and ACHE-like promoters.
In a preferred embodiment for the human ACHE gene, the promoter is a human promoter as set forth in SEQ ID No:7