Patients with Congenital Myasthenia Associated with End-plate Acetylcholinesterase Deficiency Show Normal Sequence, MRNA Splicing, and Assembly of Catalytic Subunits

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1995 Jan 1

PMID 7814634

Citations 4

Authors

S Camp

S Bon

Y Li

D K Getman

A G Engel

J Massoulie

P Taylor

Affiliations

Soon will be listed here.

Abstract

A congenital myasthenic condition has been described in several patients characterized by a deficiency in end-plate acetylcholinesterase (AChE). The characteristic form of AChE in the end-plate basal lamina has the catalytic subunits disulfide linked to a collagen-like tail unit. Southern analysis of the gene encoding the catalytic subunits revealed no differences between patient and control DNA. Genomic DNA clones covering exon 4 and the alternatively spliced exons 5 and 6 were analyzed by nuclease protection and sequencing. Although allelic differences were detected between controls, we found no differences in exonic and intronic areas that might yield distinctive splicing patterns in patients and controls. The ACHE gene was cloned from genomic libraries from a patient and a control. Transfection of the cloned genes revealed identical species of mRNA and expressed AChE. Cotransfection of the genes expressing the catalytic subunits with a cDNA from Torpedo encoding the tail unit yielded asymmetric species that require assembly of catalytic subunits and tail unit. thus the catalytic subunits of AChE expressed in the congenital myasthenic syndrome appear identical in sequence, arise from similar splicing patterns, and assemble normally with a tail unit to form a heteromeric species.

Citing Articles

Mutation in the human acetylcholinesterase-associated collagen gene, COLQ, is responsible for congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency (Type Ic).

Donger C, Krejci E, Serradell A, Eymard B, Bon S, Nicole S Am J Hum Genet. 1998; 63(4):967-75.

PMID: 9758617 PMC: 1377491. DOI: 10.1086/302059.

Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme.

Ohno K, Brengman J, Tsujino A, Engel A Proc Natl Acad Sci U S A. 1998; 95(16):9654-9.

PMID: 9689136 PMC: 21394. DOI: 10.1073/pnas.95.16.9654.

Mutations causing muscle weakness.

Lindstrom J Proc Natl Acad Sci U S A. 1998; 95(16):9070-1.

PMID: 9689034 PMC: 33876. DOI: 10.1073/pnas.95.16.9070.

Soluble monomeric acetylcholinesterase from mouse: expression, purification, and crystallization in complex with fasciculin.

Marchot P, Ravelli R, Raves M, Bourne Y, Vellom D, Kanter J Protein Sci. 1996; 5(4):672-9.

PMID: 8845756 PMC: 2143397. DOI: 10.1002/pro.5560050411.

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