The AChE membrane-binding tail PRiMA is down-regulated in muscle and nerve of mice with muscular dystrophy by merosin deficiency

Chem Biol Interact. 2013 Mar 25;203(1):330-4. doi: 10.1016/j.cbi.2012.08.001. Epub 2012 Aug 10.


Since Duchenne muscular dystrophy was attributed to mutations in the dystrophin gene, more than 30 genes have been found to be causally related with muscular dystrophies, about half of them encoding proteins of the dystrophin-glycoprotein complex (DGC). Through laminin-2, the DGC bridges the muscle cytoskeleton and the extracellular matrix. Decreased levels of PRiMA-linked acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) have been observed in dystrophic muscle and nerve of dystrophin-deficient (mdx) and laminin-2 deficient (Lama2dy) mice. To help explain these observations, the relative content of AChE, BuChE and PRiMA mRNAs were compared in normal and Lama2dy mouse muscle and sciatic nerve. The 17-fold lower level of PRiMA mRNA in Lama2dy muscle explained the deficit in PRiMA-linked ChEs. This would increase acetylcholine availability and, eventually, the desensitization of nicotinic receptors. Abnormal development of the Schwann cells led to peripheral neuropathy in the Lama2dy mouse. Compared with normal nerve, dystrophic nerve displayed 4-fold less AChE-T mRNA, 3-fold more BuChE mRNA and 2.5-fold less PRiMA mRNA, which agreed with the lower AChE activity in dystrophic nerve, its increased BuChE activity and the specific drop in PRiMA-linked BuChE. The widely accepted role of glial cells as the source of BuChE, the observed dysmyelination of Lama2dy nerve and its increased BuChE activity support the idea that BuChE up-regulation is related with the aberrant differentiation of the Schwann cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / genetics
  • Acetylcholinesterase / metabolism
  • Animals
  • Butyrylcholinesterase / genetics
  • Butyrylcholinesterase / metabolism
  • Down-Regulation
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Humans
  • Laminin / deficiency*
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Inbred mdx
  • Mice, Knockout
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / metabolism
  • Muscular Dystrophy, Animal / genetics*
  • Muscular Dystrophy, Animal / metabolism*
  • Muscular Dystrophy, Animal / pathology
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics*
  • Netrins
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Schwann Cells / metabolism
  • Schwann Cells / pathology
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / pathology


  • GPI-Linked Proteins
  • Laminin
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Netrins
  • Ntng2 protein, mouse
  • RNA, Messenger
  • laminin alpha 2
  • prima1 protein, mouse
  • Acetylcholinesterase
  • Ache protein, mouse
  • Butyrylcholinesterase

Supplementary concepts

  • Muscular dystrophy congenital, merosin negative