References
Query Results -- Details
MGI Accession ID: MGI:3790295
J Number: J:135054
Other Accession IDs:
Title: Alzheimer's presenilin 1 causes chromosome missegregation and aneuploidy.
Authors: Boeras DI; Granic A; Padmanabhan J; Crespo NC; Rojiani AM; Potter H
Journal: Neurobiol Aging
Volume: 29
Issue: 3
Date: 2008 Mar
Year: 2008
Pages: 319-28
Review Status: Peer Reviewed
Abstract:
Mutations in the presenilin 1 gene cause most early onset familial Alzheimer's disease (FAD). Here, we report that a defect in the cell cycle - improper chromosome segregation - can be caused by abnormal presenilin function and therefore may contribute to AD pathogenesis. Specifically we find that either over-expression or FAD mutation in presenilin 1 (M146L and M146V) leads to chromosome missegregation and aneuploidy in vivo and in vitro: (1) Up to 20% of lymphocytes and neurons of FAD-PS-1 transgenic and knocking mice are aneuploid by metaphase chromosome analysis and in situ hybridization. (2) Transiently transfected human cells over-expressing normal or mutant PS-1 develop similar aneuploidy within 48 h, including trisomy 21. (3) Mitotic spindles in the PS-1 transfected cells contain abnormal microtubule arrays and lagging chromosomes. Several mechanisms by which chromosome missegregation induced by presenilin may contribute to Alzheimer's disease are discussed.
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