The Determination of the Effects of Msx2 Expression on Cell Growth and Apoptotsis in Vivo
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Authors
Dalal, Neha
Issue Date
1998
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Proper skull development is dependent upon complex epithelial-mesenchymal
interactions between the developing flat bones of the calvaria and the underlying dura
mater. Craniosynostosis, a common human birth defect, occurs when calvarial sutures
prematurely fuse, causing abnormal skull development. Craniosynostosis occurs in one
out of every thousand babies born, with both genetic and environmental causes. This
birth defect is known to be a very significant biomedical burden, seeing that the only way
to cure severe craniosynsostosis is by surgical separation of the fused calvarial bones.
Studies have shown that a mutation in the homeodomain of MSX2 is associated with
Boston type craniosynostosis. This mutation causes a substitution of the amino acid
Proline with Histidine in position 7 of the MSX2 homeobox. It was hypothesized that the
mechanism by which MSX2 misregulation leads to craniosynostosis in humans and mice
may be related to preprogramlned cell death or apoptosis. This was tested by creating a
murine model of the human birth defect, by misregulatation of the wildtype or Pr07His
mutant Msx2 in transgenic mice. Both transgenic and nontransgenic mice from the same
litter were tested for the presence of apoptosis in the calvarial sutures with the Oncor
Apop Tag in situ apoptosis kit at various developmental stages. Preliminary data showed
reduced cell growth and increased apoptosis in cell populations of the sagittal suture, of
misregulated Msx2 tissues, concluding that apoptosis may be the likely mechanism by
which misregulated Msx2 leads to craniosynostosis.
Description
vi, 37 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.