Cell autonomous and cell non-autonomous effects of mosaic Mecp2 expression on layer V pyramidal cell morphology in a mouse model of Rett Syndrome
| dc.contributor.author | Rietveld, Leslie A. | |
| dc.contributor.supervisor | Delaney, Kerry R. | |
| dc.contributor.supervisor | Nahirney, Patrick C. | |
| dc.date.accessioned | 2012-12-19T19:08:26Z | |
| dc.date.available | 2012-12-19T19:08:26Z | |
| dc.date.copyright | 2012 | en_US |
| dc.date.issued | 2012-12-19 | |
| dc.degree.department | Dept. of Biology | en_US |
| dc.degree.level | Master of Science M.Sc. | en_US |
| dc.description.abstract | Rett Syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2). The mosaic brain environment in heterozygous (MECP2+/-) females consists of both MeCP2-wildtype (MeCP2+) and Mecp2-mutant (MeCP2-) neurons. To separate possible cell autonomous and cell non-autonomous effects three-dimensional morphological analysis was performed on individually genotyped layer V pyramidal neurons in the primary motor cortex of heterozygous (Mecp2+/-) and wild-type (Mecp2+/+) mature female mice (>8 months old) from the Mecp2tm1.1Jae line. Mecp2+/+ neurons and Mecp2+ were found to be indistinguishable while Mecp2- neurons have significantly reduced basal dendritic length (p<0.05), predominantly in the region 70-130 μm from the cell body, culminating in a total reduction of 15%. Mecp2- neurons have three (17%) fewer total branch points, lost specifically at the second and third branch orders. Thus the reduced total dendritic length in Mecp2- neurons is a result of fewer higher-order branches. Soma and nuclear areas of 30 Mecp2+/- female mice (5-21 months) with X chromosome inactivation (XCI) ratios ranging from 12% to 56% were analyzed. On average Mecp2- somata and nuclei were 15% and 13% smaller than Mecp2+ neurons respectively. The variation observed in the soma and nuclear sizes of Mecp2- neurons was not due to age, but was found to be correlated with the XCI ratio. Animals with a balanced XCI ratio (approximately 50% Mecp2-) were found to have Mecp2- neurons with a less severe cellular phenotype (11-17% smaller than Mecp2+). Animals with a highly skewed XCI ratio favouring expression of the wild-type allele (less than 30% Mecp2-) were found to have a more severe Mecp2- cellular phenotype (17-22% smaller than Mecp2+). These data support indicate that mutations in Mecp2 exert both cell autonomous and cell non- autonomous effects on neuronal morphology. | en_US |
| dc.description.scholarlevel | Graduate | en_US |
| dc.identifier.uri | http://hdl.handle.net/1828/4370 | |
| dc.language.iso | en | en_US |
| dc.rights.temp | Available to the World Wide Web | en_US |
| dc.subject | Rett Syndrome | en_US |
| dc.subject | Mecp2 | en_US |
| dc.subject | morphology | en_US |
| dc.subject | layer V | en_US |
| dc.subject | pyramidal | en_US |
| dc.subject | neuron | en_US |
| dc.subject | motor cortex | en_US |
| dc.subject | X-linked | en_US |
| dc.subject | X chromosome inactivation | en_US |
| dc.subject | cell autonomous | en_US |
| dc.subject | cell non-autonomous | en_US |
| dc.title | Cell autonomous and cell non-autonomous effects of mosaic Mecp2 expression on layer V pyramidal cell morphology in a mouse model of Rett Syndrome | en_US |
| dc.type | Thesis | en_US |