Accession Number:

ADA277273

Title:

The Multileveled Regulation of the Human Cholinesterase Genes and Their Protein Products

Descriptive Note:

Final rept. 30 Jul 1990-30 Jul 1993

Corporate Author:

HEBREW UNIV JERUSALEM (ISRAEL)

Personal Author(s):

Report Date:

1993-09-30

Pagination or Media Count:

176.0

Abstract:

The human ACHE and BCHE genes encoding the acetylcholine hydrolyzing enzymes acetyl- and butyrylcholinesterase AChE, BuChE were molecularly cloned and their chromosomal positions determined to be 7q22 and 3q26, respectively. Several point mutations were found in these two genes and their frequency determined within ethnically distinct populations of Israeli residents. Xenopus oocyte expression studies revealed the BuChE mutations variably alter sensitivity to inhibitors, including organophosphorous poisons. The promoter controlling ACHE gene expression was characterized and shown to direct the expression of human AChE in developing myotomes from transiently transgenic Xenopus laevis embryos, where the transgenic enzyme faithfully accumulated in neuromuscular junctions. Alternative splicing in ACHEmRNA transcripts was found to lead to 3 distinct enzyme forms, 2 of which are abundant in tumors. Antisense phosphorothioate oligodeoxynucleotide-targetted destruction of ACHEmRNA in mice was found to cause transient hematopoietic alterations, notably reduced erythrocyte counts. Acetylcholinesterase, Butyrylcholinesterase, DNA sequencing, Alternative splicing, Natural variants, Xenopus expression, Site-directed mutagenesis

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE