Skeletal and CNS defects in Presenilin-1-deficient mice

Jie Shen, Roderick T. Bronson, Dong Feng Chen, Weiming Xia, Dennis J. Selkoe, Susumu Tonegawa

Research output: Contribution to journalArticlepeer-review

866 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)629-639
Number of pages11
Issue number4
StatePublished - May 16 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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