Constitutive notch signaling in adult transgenic mice inhibits bFGF-induced angiogenesis and blocks ovarian follicle development

Liu, Ju; Deutsch, Urban; Jeong, James; Lobe, Corrinne G (2014). Constitutive notch signaling in adult transgenic mice inhibits bFGF-induced angiogenesis and blocks ovarian follicle development. Genesis, 52(9), pp. 809-816. Wiley-Liss 10.1002/dvg.22790

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Notch signaling is important in angiogenesis during embryonic development. However, the embryonic lethal phenotypes of knock-out and transgenic mice have precluded studies of the role of Notch post-natally. To develop a mouse model that would bypass the embryonic lethal phenotype and investigate the possible role of Notch signaling in adult vessel growth, we developed transgenic mice with Cre-conditional expression of the constitutively active intracellular domain of Notch1 (IC-Notch1). Double transgenic IC-Notch1/Tie2-Cre embryos with endothelial specific IC-Notch1 expression died at embryonic day 9.5. They displayed collapsed and leaky blood vessels and defects in angiogenesis development. A tetracycline-inducible system was used to express Cre recombinase postnatally in endothelial cells. In adult mice, IC-Notch1 expression inhibited bFGF-induced neovascularization and female mice lacked mature ovarian follicles, which may reflect the block in bFGF-induced angiogenesis required for follicle growth. Our results demonstrate that Notch signaling is important for both embryonic and adult angiogenesis and indicate that the Notch signaling pathway may be a useful target for angiogenic therapies.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Deutsch, Urban

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1526-954X

Publisher:

Wiley-Liss

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

07 Apr 2015 13:31

Last Modified:

19 Nov 2015 10:38

Publisher DOI:

10.1002/dvg.22790

PubMed ID:

24817584

Uncontrolled Keywords:

angiogenesis, Notch signaling, basic FGF, follicular development, transgenic mice

BORIS DOI:

10.7892/boris.66372

URI:

https://boris.unibe.ch/id/eprint/66372

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