Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein

Kang Woo Lee, Joo Young Im, Jin Sook Song, Si Hyoung Lee, Ho Jeong Lee, Hye Yeong Ha, Jae Young Koh, Byoung Joo Gwag, Sung Don Yang, Sang Gi Paik, Pyung Lim Han

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The β-secretase cleaved Aβ-bearing carboxy-terminal fragments (βCTFs) of amyloid precursor protein (APP) in neural cells have been suggested to be cytotoxic. However, the functional significance of βCTFs in vivo remains elusive. We created a transgenic mouse line Tg-βCTF99/B6 expressing the human βCTF99 in the brain of inbred C57BL/6 strain. Tg-βCTF99/B6 mouse brain at 12-16 months showed severely down-regulated calbindin, phospho-CREB, and Bcl-xL expression and up-regulated phospho-JNK, Bcl-2, and Bax expression. Neuronal cell density in the Tg-βCTF99/B6 cerebral cortex at 16-18 months was lower than that of the non-transgenic control, but not at 5 months. At 11-14 months, Tg-βCTF99/B6 mice displayed cognitive impairments and increased anxiety, which were not observed at 5 months. These results suggest that increased βCTF99 expression is highly detrimental to the aging brain and that it produces a progressive and age-dependent AD-like pathogenesis.

Original languageEnglish
Pages (from-to)10-24
Number of pages15
JournalNeurobiology of Disease
Volume22
Issue number1
DOIs
StatePublished - Apr 2006

Keywords

  • AD model
  • Cognitive deficits
  • CTF
  • Neuronal loss
  • Transgenic animal

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