Enlarged brain ventricles and impaired neurogenesis in the Ts1Cje and Ts2Cje mouse models of Down syndrome.
Down syndrome (DS) is the most common cause of mental retardation. Although structural and neurogenic abnormalities have been shown in the brains of DS patients, the molecular etiology is still unknown. To define it, we have performed structural and histological examinations of the brains of Ts1Cje and Ts2Cje, 2 mouse models for DS. These mice carry different length of trisomic segments of mouse chromosome 16 that are orthologous to human chromosome 21. At 3 months of age, ventricular enlargements were observed in both Ts1Cje and Ts2Cje brains at a similar degree. Both mice also showed decreases of the number of doublecortin-positive neuroblasts and thymidine-analog BrdU-labeled proliferating cells in the subventricular zone of the lateral ventricles (LVs) and in the hippocampal dentate gyrus at a similar degree, suggesting impaired adult neurogenesis. Additionally, at embryonic day 14.5, both strains of mice, when compared with diploid littermates, had smaller brains and decreased cortical neurogenesis that could possibly contribute to the ventricular enlargements observed in adulthood. Our findings suggest that the trisomic segment of the Ts1Cje mouse, which is shared with Ts2Cje, contains the genes that are responsible for these abnormal phenotypes and could be relevant to the mental retardation associated with DS.
Ishihara
Keiichi
K
Laboratory for Neurogenetics, RIKEN, Brain Science Institute, Saitama 351-0198, Japan.
Amano
Kenji
K
Takaki
Eiichi
E
Shimohata
Atsushi
A
Sago
Haruhiko
H
Epstein
Charles J
CJ
Yamakawa
Kazuhiro
K
D000818:Animals; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000196:embryology / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D002891:Chromosomes, Human, Pair 21; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis; D009479:Neuropeptides / Q000378:metabolism; D011247:Pregnancy; D014314:Trisomy / Q000235:genetics* / Q000503:physiopathology*
D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides