title: Abnormal blood vessel development in mice lacking presenilin-1.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, 173-0015 Tokyo, Japan.
authors.forename: Mitsunari
authors.initials: M
authors.lastname: Nakajima
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yuasa
authors.forename: Masaya
authors.initials: M
authors.lastname: Ueno
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Takuji
authors.initials: T
authors.lastname: Shirasawa
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology* / Q000378:metabolism; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000002:abnormalities / Q000166:cytology; D002543:Cerebral Hemorrhage / Q000235:genetics / Q000378:metabolism; D004487:Edema / Q000235:genetics / Q000378:metabolism; D004727:Endothelium / Q000002:abnormalities / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D053764:Presenilin-1
chemical_list: D008565:Membrane Proteins; D053764:Presenilin-1