Increased dosage of DYRK1A and brain volumetric alterations in a YAC model of partial trisomy 21.
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%).
Sebrié
Catherine
C
Laboratoire de RMN Biologique, ICSN-CNRS, Gif sur Yvette, France.
Chabert
Caroline
C
Ledru
Aurélie
A
Guedj
Fayçal
F
Po
Chrystelle
C
Smith
Desmond J
DJ
Rubin
Edward
E
Rivals
Isabelle
I
Beloeil
Jean-Claude
JC
Gillet
Brigitte
B
Delabar
Jean-Maurice
JM
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology / Q000473:pathology*; D018244:Chromosomes, Artificial, Yeast; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D007031:Hypothalamus / Q000201:enzymology / Q000473:pathology; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D013788:Thalamus / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation; D000097603:Dyrk Kinases
D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases