Alterations in the Phenotype of Neocortical Pyramidal Cells in the Dyrk1A+/- Mouse

Neurobiol Dis. 2005 Oct;20(1):115-22. doi: 10.1016/j.nbd.2005.02.004.

Abstract

The gene encoding the dual-specificity tyrosine-regulated kinase DYRK1A maps to the chromosomal segment HSA21q22.2, which lies within the Down syndrome critical region. The reduction in brain size and behavioral defects observed in mice lacking one copy of the murine homologue Dyrk1A (Dyrk1A+/-) support the idea that this kinase may be involved in monosomy 21 associated mental retardation. However, the structural basis of these behavioral defects remains unclear. In the present work, we have analyzed the microstructure of cortical circuitry in the Dyrk1A+/- mouse and control littermates by intracellular injection of Lucifer Yellow in fixed cortical tissue. We found that labeled pyramidal cells were considerably smaller, less branched and less spinous in the cortex of Dyrk1A+/- mice than in control littermates. These results suggest that Dyrk1A influences the size and complexity of pyramidal cells, and thus their capability to integrate information.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Shape / genetics
  • Dendritic Spines / metabolism
  • Dendritic Spines / pathology
  • Disease Models, Animal
  • Down Syndrome / genetics
  • Down Syndrome / pathology
  • Down Syndrome / physiopathology
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neocortex / abnormalities*
  • Neocortex / metabolism
  • Neocortex / pathology*
  • Nervous System Malformations / genetics*
  • Nervous System Malformations / metabolism
  • Nervous System Malformations / pathology
  • Phenotype
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Tyrosine Kinases
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / pathology*

Substances

  • Dyrk kinase
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases