TY - JOUR
T1 - Skeletal and CNS defects in Presenilin-1-deficient mice
AU - Shen, Jie
AU - Bronson, Roderick T.
AU - Chen, Dong Feng
AU - Xia, Weiming
AU - Selkoe, Dennis J.
AU - Tonegawa, Susumu
N1 - Funding Information:
We thank David Gerber and Ray Kelleher for discussions and critical reading of the manuscript; Yukang Wang for help with the skeletal preparations and discussions; Janice Williams, Kim Mercer, and Denise Crowley for histological technical help; En Li and Hong Lei for the J1 embryonic stem cells and advice on their proper handling; Haydn Prosser for the mouse brain cDNA library; Oksana Berezovska, Brad Hyman, Bernhard Bader, Richard Hynes, Tom Wisniewski, Martin Hrabe de Angelis, and Achim Gossler for sharing unpublished results; Matt Frosch and Matt Anderson for advice on neuropathology; Dennis King for managerial help; and Emily Rossie and Pam Woronoff for secretarial help. We are grateful to members of the Tonegawa lab, Haydn Prosser, Josh Huang, Lydia Nelson, Toshikuni Sasaoka, Ming Xu, Takuji Iwasato, Ken Poss, Min Wu, and Kazutoshi Nakazawa, for discussions and technical help. This work was supported by NIH grant #NS32925 and gifts from the Shionogi Institute for Medical Science and Amgen, Inc. (to S. T.), and by NIH grant #AG06173 (to D. J. S.). J. S. is supported by a postdoctoral fellowship from the Leukemia Society of America.
PY - 1997/5/16
Y1 - 1997/5/16
N2 - Presenilin-1 (PS1) is the major gene responsible for early-onset familial Alzheimer's disease (FAD). To understand the normal function of PS1, we have generated a targeted null mutation in the murine homolog of PS1. We report that PS1(-/-) mice die shortly after natural birth or Caesarean section. The skeleton of homozygous mutants is grossly deformed. Hemorrhages occur in the CNS of PS1 null mutants with varying location, severity, and time of onset. The ventricular zone of PS1(-/-) brains is markedly thinner by embryonic day 14.5, indicating an impairment in neurogenesis. Bilateral cerebral cavitation caused by massive neuronal loss in specific subregions of the mutant brain is prominent after embryonic day 16.5. These results show that PS1 is required for proper formation of the axial skeleton, normal neurogenesis, and neuronal survival.
AB - Presenilin-1 (PS1) is the major gene responsible for early-onset familial Alzheimer's disease (FAD). To understand the normal function of PS1, we have generated a targeted null mutation in the murine homolog of PS1. We report that PS1(-/-) mice die shortly after natural birth or Caesarean section. The skeleton of homozygous mutants is grossly deformed. Hemorrhages occur in the CNS of PS1 null mutants with varying location, severity, and time of onset. The ventricular zone of PS1(-/-) brains is markedly thinner by embryonic day 14.5, indicating an impairment in neurogenesis. Bilateral cerebral cavitation caused by massive neuronal loss in specific subregions of the mutant brain is prominent after embryonic day 16.5. These results show that PS1 is required for proper formation of the axial skeleton, normal neurogenesis, and neuronal survival.
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U2 - 10.1016/S0092-8674(00)80244-5
DO - 10.1016/S0092-8674(00)80244-5
M3 - Article
C2 - 9160754
AN - SCOPUS:0030779784
SN - 0092-8674
VL - 89
SP - 629
EP - 639
JO - Cell
JF - Cell
IS - 4
ER -