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Publication : Abnormal blood vessel development in mice lacking presenilin-1.

First Author  Nakajima M Year  2003
Journal  Mech Dev Volume  120
Issue  6 Pages  657-67
PubMed ID  12834865 Mgi Jnum  J:84418
Mgi Id  MGI:2667569 Doi  10.1016/s0925-4773(03)00064-9
Citation  Nakajima M, et al. (2003) Abnormal blood vessel development in mice lacking presenilin-1. Mech Dev 120(6):657-67
abstractText  Presenilin-1 (PS1) is a gene responsible for the development of early-onset familial Alzheimer's disease. To explore the potential roles of PS1 in vascular development, we examined the vascular system of mouse embryos lacking PS1. PS1-deficient embryos exhibited cerebral hemorrhages and subcutaneous edema by mid gestation. Immunohistochemical analysis revealed vascular remodeling failure in the stomach and trunk dorsal median region of the skin and insufficient formation of the perineural plexus around the spinal cord of the PS1 mutant embryos. The number of capillary sprouting sites reduced and the capillary diameter increased in the mutant brains, especially at the amygdaloid and striatal regions. Endothelial cells in the sprouting capillaries of the mutant mice showed abnormal morphologies such as multiplication, apoptotic and necrotic images, in contrast to pericytes showing a normal appearance. An in vitro assay using para-aortic splanchnopleural mesoderm (P-Sp) revealed aberrant angiogenesis in the explant culture from the mutant. These findings suggest the essential roles of PS1 in angiogenesis.
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