Loss of nicastrin elicits an apoptotic phenotype in mouse embryos

Brain Research
Van NguyenRichard F Rozmahel

Abstract

Nicastrin is a member of the high molecular weight presenilin complex that plays a central role in gamma-secretase cleavage of numerous type-1 membrane-associated proteins required for cell signaling, proliferation and lineage development. We have generated a nicastrin-null mouse line by disruption of exon 3. Similar to previously described nicastrin-null mice, these animals demonstrate severe growth retardation, mortality beginning at embryonic age 10.5 days, and marked developmental abnormalities indicative of a severe Notch phenotype. Preceding their mortality, 10.5-day-old nicastrin-null embryos were found to also exhibit specific apoptosis within regions showing profound deformities, particularly in the developing heart and brain. This result suggests that complete disruption of presenilin complexes elicits programmed cell death, in addition to a Notch phenotype, which may contribute to the developmental abnormalities and embryonic mortality of nicastrin-null mice and possibly neurodegeneration in Alzheimer's disease.

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Citations

Apr 19, 2013·Molecular Neurobiology·Jun Seo GooDae Youn Hwang
Jan 6, 2009·Biochemistry. Biokhimii︠a︡·Lan-Tu GouYu-Quan Wei
Jun 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Katsuhiko TabuchiJie Shen
Feb 5, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Guojun ZhaoRaphael Kopan
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Apr 21, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jane McLeodPaul G Genever

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