Alzheimer-associated mutant ubiquitin impairs spatial reference memory

Paula van Tijn, Barbara Hobo, Marian C. Verhage, Melly S. Oitzl, Fred W. van Leeuwen, David F. Fischer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


UBB+1 is a mutant ubiquitin which accumulates in the hallmarks of tauopathies, including Alzheimer's disease. Transgenic mice expressing high levels of neuronal UBB+1 exhibit moderately decreased proteasome activity and spatial reference memory deficits at 9 months of age. In the present study, we characterized the behavioral phenotype of male UBB+1 transgenic mice at different ages. We show that UBB+1 transgenic mice displayed an age-related functional decline similar to wild-type littermates, without gross neurological abnormalities or alterations in procedural motor-learning and motor coordination. At 15 months of age, a transgene-specific spatial learning deficit was dependent on the period of training in the Morris watermaze. This deficit could be eliminated after additional training. We conclude that the previously reported spatial reference memory deficits of UBB+1 transgenic mice persist during aging. In addition, our results demonstrate that the subtle defect in spatial reference memory formation, caused by a decrease in forebrain proteasome activity, is a persistent defect and not a structural defect.
Original languageEnglish
Pages (from-to)193-200
JournalPhysiology & Behavior
Issue number2
Publication statusPublished - 1 Feb 2011


  • Ubiquitin-proteasome system
  • Neurodegeneration
  • Transgenic mouse model
  • Mutant ubiquitin
  • Behavior

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