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Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein.
Neurobiol Dis. 2006 Apr; 22(1):10-24.ND

Abstract

The beta-secretase cleaved Abeta-bearing carboxy-terminal fragments (betaCTFs) of amyloid precursor protein (APP) in neural cells have been suggested to be cytotoxic. However, the functional significance of betaCTFs in vivo remains elusive. We created a transgenic mouse line Tg-betaCTF99/B6 expressing the human betaCTF99 in the brain of inbred C57BL/6 strain. Tg-betaCTF99/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-betaCTF99/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-betaCTF99/B6 mice displayed cognitive impairments and increased anxiety, which were not observed at 5 months. These results suggest that increased betaCTF99 expression is highly detrimental to the aging brain and that it produces a progressive and age-dependent AD-like pathogenesis.

Authors+Show Affiliations

Department of Neuroscience, Neuroscience Research Center and Medical Research Institute, Ewha Womans University School of Medicine, 911-1 Mok-6-Dong, Yangchun-Gu, Seoul 158-710, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16289866

Citation

Lee, Kang-Woo, et al. "Progressive Neuronal Loss and Behavioral Impairments of Transgenic C57BL/6 Inbred Mice Expressing the Carboxy Terminus of Amyloid Precursor Protein." Neurobiology of Disease, vol. 22, no. 1, 2006, pp. 10-24.
Lee KW, Im JY, Song JS, et al. Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein. Neurobiol Dis. 2006;22(1):10-24.
Lee, K. W., Im, J. Y., Song, J. S., Lee, S. H., Lee, H. J., Ha, H. Y., Koh, J. Y., Gwag, B. J., Yang, S. D., Paik, S. G., & Han, P. L. (2006). Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein. Neurobiology of Disease, 22(1), 10-24.
Lee KW, et al. Progressive Neuronal Loss and Behavioral Impairments of Transgenic C57BL/6 Inbred Mice Expressing the Carboxy Terminus of Amyloid Precursor Protein. Neurobiol Dis. 2006;22(1):10-24. PubMed PMID: 16289866.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein. AU - Lee,Kang-Woo, AU - Im,Joo-Young, AU - Song,Jin-Sook, AU - Lee,Si Hyoung, AU - Lee,Ho-Jeong, AU - Ha,Hye-Yeong, AU - Koh,Jae-Young, AU - Gwag,Byoung Joo, AU - Yang,Sung-Don, AU - Paik,Sang-Gi, AU - Han,Pyung-Lim, Y1 - 2005/11/11/ PY - 2004/09/23/received PY - 2005/09/23/revised PY - 2005/09/27/accepted PY - 2005/11/18/pubmed PY - 2006/6/2/medline PY - 2005/11/18/entrez SP - 10 EP - 24 JF - Neurobiology of disease JO - Neurobiol Dis VL - 22 IS - 1 N2 - The beta-secretase cleaved Abeta-bearing carboxy-terminal fragments (betaCTFs) of amyloid precursor protein (APP) in neural cells have been suggested to be cytotoxic. However, the functional significance of betaCTFs in vivo remains elusive. We created a transgenic mouse line Tg-betaCTF99/B6 expressing the human betaCTF99 in the brain of inbred C57BL/6 strain. Tg-betaCTF99/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-betaCTF99/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-betaCTF99/B6 mice displayed cognitive impairments and increased anxiety, which were not observed at 5 months. These results suggest that increased betaCTF99 expression is highly detrimental to the aging brain and that it produces a progressive and age-dependent AD-like pathogenesis. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/16289866/Progressive_neuronal_loss_and_behavioral_impairments_of_transgenic_C57BL/6_inbred_mice_expressing_the_carboxy_terminus_of_amyloid_precursor_protein_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(05)00267-6 DB - PRIME DP - Unbound Medicine ER -