Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene

Cell. 1994 Dec 2;79(5):755-65. doi: 10.1016/0092-8674(94)90066-3.


The beta-amyloid precursor protein (beta APP) gene of the mouse was disrupted by inserting into exon 2 a cassette containing a neomycin resistance gene and a putative transcription termination sequence. Contrary to expectation, brain and other tissues from mice homozygous for the insertion still contained beta APP-specific RNA, albeit at a level 5- to 10-fold lower than wild type and lacking the disrupted exon, which had been spliced out. The brain contained shortened beta APP-specific protein at a low level. Mutant mice were severely impaired in spatial learning and exploratory behavior and showed increased incidence of agenesis of the corpus callosum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Protein Precursor / genetics*
  • Animals
  • Base Sequence
  • Behavior, Animal*
  • Brain / pathology*
  • Exons / genetics
  • Exploratory Behavior
  • Female
  • Gene Expression
  • Homozygote
  • Learning
  • Male
  • Mice
  • Mice, Mutant Strains*
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • RNA, Messenger / analysis
  • Spatial Behavior


  • Amyloid beta-Protein Precursor
  • RNA, Messenger