Patients with congenital myasthenia associated with end-plate acetylcholinesterase deficiency show normal sequence, mRNA splicing, and assembly of catalytic subunits

S. Camp, S. Bon, Y. Li, D. K. Getman, Andrew G Engel, J. Massoulie, P. Taylor

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)333-340
Number of pages8
JournalJournal of Clinical Investigation
Volume95
Issue number1
StatePublished - 1995
Externally publishedYes

Fingerprint

Congenital Myasthenic Syndromes
Acetylcholinesterase
Catalytic Domain
Tail
Messenger RNA
Genes
Exons
Torpedo
Genomic Library
DNA
Muscle Weakness
Basement Membrane
Disulfides
Transfection
Collagen
Complementary DNA
Clone Cells

Keywords

  • acetylcholinesterase species
  • alternative mRNA processing
  • collagenous subunit
  • congenital acetylcholinesterase deficiency
  • myasthenic syndrome

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Patients with congenital myasthenia associated with end-plate acetylcholinesterase deficiency show normal sequence, mRNA splicing, and assembly of catalytic subunits. / Camp, S.; Bon, S.; Li, Y.; Getman, D. K.; Engel, Andrew G; Massoulie, J.; Taylor, P.

In: Journal of Clinical Investigation, Vol. 95, No. 1, 1995, p. 333-340.

Research output: Contribution to journalArticle

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AU - Camp, S.

AU - Bon, S.

AU - Li, Y.

AU - Getman, D. K.

AU - Engel, Andrew G

AU - Massoulie, J.

AU - Taylor, P.

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