Breaches of the pial basement membrane are associated with defective dentate gyrus development in mouse models of congenital muscular dystrophies

Neurosci Lett. 2011 Nov 7;505(1):19-24. doi: 10.1016/j.neulet.2011.09.040. Epub 2011 Sep 29.

Abstract

A subset of congenital muscular dystrophies (CMDs) has central nervous system manifestations. There are good mouse models for these CMDs that include POMGnT1 knockout, POMT2 knockout and Large(myd) mice with all exhibiting defects in dentate gyrus. It is not known how the abnormal dentate gyrus is formed during the development. In this study, we conducted a detailed morphological examination of the dentate gyrus in adult and newborn POMGnT1 knockout, POMT2 knockout, and Large(myd) mice by immunofluorescence staining and electron microscopic analyses. We observed that the pial basement membrane overlying the dentate gyrus was disrupted and there was ectopia of granule cell precursors through the breached pial basement membrane. Besides these, the knockout dentate gyrus exhibited reactive gliosis in these mouse models. Thus, breaches in the pial basement membrane are associated with defective dentate gyrus development in mouse models of congenital muscular dystrophies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / abnormalities*
  • Basement Membrane / metabolism
  • Basement Membrane / ultrastructure
  • Dentate Gyrus / pathology*
  • Disease Models, Animal
  • Gene Expression Regulation / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosis / genetics
  • Gliosis / pathology
  • Homeodomain Proteins / metabolism
  • Mannosyltransferases / genetics
  • Mannosyltransferases / metabolism
  • Mice
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophies / pathology*
  • N-Acetylglucosaminyltransferases / deficiency
  • N-Acetylglucosaminyltransferases / genetics
  • Pia Mater / metabolism
  • Pia Mater / pathology*
  • Pia Mater / ultrastructure
  • Tumor Suppressor Proteins / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • Homeodomain Proteins
  • Tumor Suppressor Proteins
  • prospero-related homeobox 1 protein
  • Large1 protein, mouse
  • Mannosyltransferases
  • N-Acetylglucosaminyltransferases
  • protein O-mannose beta-1,2-N-acetylglucosaminyltransferase
  • protein O-mannosyltransferase