Skeletal and CNS defects in Presenilin-1-deficient mice

Cell. 1997 May 16;89(4):629-39. doi: 10.1016/s0092-8674(00)80244-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics
  • Animals
  • Base Sequence
  • Bone and Bones / abnormalities*
  • Bone and Bones / embryology
  • Central Nervous System / abnormalities*
  • Central Nervous System / embryology
  • Cerebral Hemorrhage / genetics
  • DNA Primers / genetics
  • Gestational Age
  • Humans
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology
  • Mice
  • Mice, Knockout
  • Mutation
  • Nerve Degeneration / genetics
  • Phenotype
  • Presenilin-1


  • DNA Primers
  • Membrane Proteins
  • PSEN1 protein, human
  • Presenilin-1