Increased dosage of DYRK1A and brain volumetric alterations in a YAC model of partial trisomy 21

Anat Rec (Hoboken). 2008 Mar;291(3):254-62. doi: 10.1002/ar.20640.

Abstract

A yeast artificial chromosome (YAC) transgenic murine model of partial trisomy 21 overexpressing five human genes -- including DYRK1A, which encodes a serine threonine kinase involved in cell cycle control -- has been shown to present an increase in brain weight. We analyzed this new phenotype by measuring total and regional brain volumes at different ages, using a 7 Tesla magnetic resonance imaging volumetric approach. Volumetric measurements showed a total volume increase of 13.6% in adult mice. Changes in brain morphogenesis were already visible at a very early postnatal stage (postnatal days 2-7). Region-specific changes were characterized from postnatal day 15 to 5 months. These results, made it possible to define region-specific effects of DYRK1A overexpression, with the strongest increase seen in the thalamus-hypothalamus area (24%).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / genetics
  • Aging / pathology
  • Animals
  • Animals, Newborn
  • Brain / enzymology
  • Brain / pathology*
  • Chromosomes, Artificial, Yeast*
  • Disease Models, Animal
  • Down Syndrome / enzymology
  • Down Syndrome / genetics*
  • Down Syndrome / pathology
  • Dyrk Kinases
  • Gene Dosage*
  • Genotype
  • Humans
  • Hypothalamus / enzymology
  • Hypothalamus / pathology
  • Imaging, Three-Dimensional
  • Magnetic Resonance Imaging*
  • Mice
  • Mice, Transgenic
  • Organ Size
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Thalamus / enzymology
  • Thalamus / pathology
  • Up-Regulation

Substances

  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases