Expression of genes related to muscular dystrophy with lissencephaly

Pediatr Neurol. 2004 Sep;31(3):183-90. doi: 10.1016/j.pediatrneurol.2004.03.020.

Abstract

There is a group of congenital muscular dystrophies accompanying the brain lesions termed cobblestone lissencephaly. Abnormal glia limitans could be considered the major pathogenesis of cobblestone lissencephaly. In this group, protein-O-linked mannose-beta1,2-N-acetylglucosaminyltransferase and protein-O-mannosyltransferase 1 are considered to be responsible for muscle-eye-brain disease and Walker-Warburg syndrome, respectively, by glycosylation of alpha-dystroglycan. However, the functions of fukutin, a gene responsible for Fukuyama type congenital muscular dystrophy, are still unclear. In this study, expression of the three aforementioned genes was compared by in situ hybridization in control cases to elucidate the functions of fukutin. Immunohistochemistry of fukutin and alpha-dystroglycan was also performed. In the central nervous system, all three genes were expressed in astrocytes and in immature neurons. A few mature neurons expressed fukutin, but many expressed the other two genes. All genes were expressed in various non-nervous tissues including tissues relating to secretion. Fukutin and alpha-dystroglycan were generally colocalized, but localization was not always the same, especially in the liver. Fukutin may be associated with the glycosylation of alpha-dystroglycan, and expression in astrocytes may indicate a relation to glia limitans. The roles of fukutin in mature neurons may be less critical compared with the other two genes. Additional functions of fukutin, especially in the liver, are suspected.

MeSH terms

  • Adolescent
  • Adult
  • Brain / metabolism
  • Brain / pathology
  • Fetal Diseases / genetics
  • Gene Expression Regulation*
  • Humans
  • Membrane Proteins
  • Middle Aged
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophies / metabolism
  • Muscular Dystrophies / pathology
  • N-Acetylglucosaminyltransferases / biosynthesis
  • N-Acetylglucosaminyltransferases / genetics
  • Pentosyltransferases
  • Proteins / genetics
  • Proteins / metabolism

Substances

  • FKTN protein, human
  • Membrane Proteins
  • Proteins
  • N-Acetylglucosaminyltransferases
  • protein O-mannose beta-1,2-N-acetylglucosaminyltransferase
  • FKRP protein, human
  • Pentosyltransferases