Neuroscience 2004 Abstract
| Presentation Number: | 482.1 |
|---|---|
| Abstract Title: | Alterations of brain morphogenesis in murine models of Down syndrome. |
| Authors: |
Delabar, J. M.*1
; Chabert, C.1
; Sebrie, C.2
; Bichler, Z.3
; Rachidi, M.1
; Lopes, C.1
; Ledru, A.1
; Paly, E.1
; Gillet, B.2
; Rubin, E.
; Branchi, I.
1EA3508, Université Paris7, Paris, France 2France, case 7104, 2 place Jussieu, 75251, 3ICSN-CNRS, case 7104, 2 place Jussieu, 75251, |
| Primary Theme and Topics |
Development - Neurogenesis and Gliogenesis -- Proliferation |
| Session: |
482. CNS Neurogenesis Slide |
| Presentation Time: | Monday, October 25, 2004 1:00 PM-1:15 PM |
| Location: | San Diego Convention Center - Room 11B |
| Keywords: | DOWN SYNDROME, MODELING, NEUROGENESIS, SIGNAL TRANSDUCTION |
Study of human partial trisomies has indicated that gene(s) from the DCR-1 region (CBR1-ERG) should be involved in facial and hand features and in mental retardation observed in Down syndrome. Smith et al have constructed low copy number transgenic mice containing four different human yeast artificial chromosomes that together covered approximately 2Mb (ie 80%) of DCR-1; this panel constitutes an in vivo library for phenotype screening.
We carried out a neuropathological study of these transgenic lines and found that the integration of two of these YACs, 230-e8 and 152-f7 caused morphogenetic changes: YAC 230-e8 mice showed an abnormal cerebellar folial pattern, a decrease in transverse diameter of the cerebellum and an increase in cortical cell density; YAC 152-f7 mice showed an increase in brain weight and a clear learning impairment. The brain weight increase was further explored by using magnetic resonance imaging (MRI): this technique allows to follow brain changes along animal development.
Interestingly the volumetric measurements, which were done on a 7T/20cm horizontal MRI scanner (Varian) using an image-processing software, showed that a total volume increase (17% in adult mice), already observable at P7, corresponded to region specific changes with the strongest increase for the thalamus-hypothalamus region ( more than 30%). Moreover in brains of 152f7 mice, Dyrk1a, a serine threonine kinase, as well as other genes carried by the YAC, was found overexpressed both at RNA and protein levels. One of the dyrk1a targets, the transcription factors fkhr, showed an increased phosphorylation associated with increased levels of cyclin B1. These results evidenced that the DCR-1 contains important genes involved in brain morphogenesis and neurogenesis and that the study of their overexpression might unravel new signaling pathways modified in DS.
We carried out a neuropathological study of these transgenic lines and found that the integration of two of these YACs, 230-e8 and 152-f7 caused morphogenetic changes: YAC 230-e8 mice showed an abnormal cerebellar folial pattern, a decrease in transverse diameter of the cerebellum and an increase in cortical cell density; YAC 152-f7 mice showed an increase in brain weight and a clear learning impairment. The brain weight increase was further explored by using magnetic resonance imaging (MRI): this technique allows to follow brain changes along animal development.
Interestingly the volumetric measurements, which were done on a 7T/20cm horizontal MRI scanner (Varian) using an image-processing software, showed that a total volume increase (17% in adult mice), already observable at P7, corresponded to region specific changes with the strongest increase for the thalamus-hypothalamus region ( more than 30%). Moreover in brains of 152f7 mice, Dyrk1a, a serine threonine kinase, as well as other genes carried by the YAC, was found overexpressed both at RNA and protein levels. One of the dyrk1a targets, the transcription factors fkhr, showed an increased phosphorylation associated with increased levels of cyclin B1. These results evidenced that the DCR-1 contains important genes involved in brain morphogenesis and neurogenesis and that the study of their overexpression might unravel new signaling pathways modified in DS.
Supported by IBANGS
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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