Tags

Type your tag names separated by a space and hit enter

Progressive cognitive impairment and anxiety induction in the absence of plaque deposition in C57BL/6 inbred mice expressing transgenic amyloid precursor protein.
J Neurosci Res. 2004 May 15; 76(4):572-80.JN

Abstract

Numerous transgenic mouse models for Alzheimer's disease (AD) have been generated to recapitulate the histological pathogenesis and behavioral phenotypes of AD brain. However, none of the existing models exhibits the full spectrum of AD symptoms, nor have all of the traits mimicked by the developed animal models been successfully represented within a single mouse line, indicating that the development of transgenic lines showing new features of the AD-like brain should be explored. Here we report on a transgenic mouse line, named Tg-APP (Sw, V717F)/B6, that expresses the human amyloid precursor protein (APP) containing the Swedish and the V717F Indiana mutations in the brains of inbred C57BL/6 mice, designed to eliminate the potential phenotypic variations attributed to the compound genetic backgrounds adopted in most AD mouse models. The Tg-APP (Sw, V717F)/B6 mice expressed the transgene transcript, in the heterozygote state, at a level of 2.6 +/- 0.1 fold higher than that of endogenous mouse APP. However, no Abeta-plaque deposition was produced in the brain of the Tg-APP (Sw, V717F)/B6 mice up to 18 months of age. The Tg-APP(Sw, V717F)/B6 mice at 13-15 months showed reduced expression of calbindin and c-Fos in the brain. The Tg-APP (Sw, V717F)/B6 mice at 11-14 months displayed decreased motor coordination, learning and memory deficits, and severely increased anxiety. These phenotypes were not observed in the Tg-APP (Sw, V717F)/B6 mice at 5-7 months. Microarray analysis revealed altered expression, in the amygdala of the Tg-APP (Sw, V717F)/B6 mice, of genes previously implicated in anxiety. Taken together, these results suggest that the transgenic APP, or its derivatives, produces the age-dependent pathophysiology of the AD-like brain and that the progressive cognitive impairment and anxiety induction can proceed in the absence of visible Abeta-plaque deposition.

Authors+Show Affiliations

Department of Neuroscience, Ewha Institute of Neuroscience and Medical Research Institute, Ewha Womans University School of Medicine, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15114629

Citation

Lee, Kang-Woo, et al. "Progressive Cognitive Impairment and Anxiety Induction in the Absence of Plaque Deposition in C57BL/6 Inbred Mice Expressing Transgenic Amyloid Precursor Protein." Journal of Neuroscience Research, vol. 76, no. 4, 2004, pp. 572-80.
Lee KW, Lee SH, Kim H, et al. Progressive cognitive impairment and anxiety induction in the absence of plaque deposition in C57BL/6 inbred mice expressing transgenic amyloid precursor protein. J Neurosci Res. 2004;76(4):572-80.
Lee, K. W., Lee, S. H., Kim, H., Song, J. S., Yang, S. D., Paik, S. G., & Han, P. L. (2004). Progressive cognitive impairment and anxiety induction in the absence of plaque deposition in C57BL/6 inbred mice expressing transgenic amyloid precursor protein. Journal of Neuroscience Research, 76(4), 572-80.
Lee KW, et al. Progressive Cognitive Impairment and Anxiety Induction in the Absence of Plaque Deposition in C57BL/6 Inbred Mice Expressing Transgenic Amyloid Precursor Protein. J Neurosci Res. 2004 May 15;76(4):572-80. PubMed PMID: 15114629.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progressive cognitive impairment and anxiety induction in the absence of plaque deposition in C57BL/6 inbred mice expressing transgenic amyloid precursor protein. AU - Lee,Kang-Woo, AU - Lee,Si Hyoung, AU - Kim,Hyuck, AU - Song,Jin-Sook, AU - Yang,Sung-Don, AU - Paik,Sang Gi, AU - Han,Pyung-Lim, PY - 2004/4/29/pubmed PY - 2004/6/23/medline PY - 2004/4/29/entrez SP - 572 EP - 80 JF - Journal of neuroscience research JO - J Neurosci Res VL - 76 IS - 4 N2 - Numerous transgenic mouse models for Alzheimer's disease (AD) have been generated to recapitulate the histological pathogenesis and behavioral phenotypes of AD brain. However, none of the existing models exhibits the full spectrum of AD symptoms, nor have all of the traits mimicked by the developed animal models been successfully represented within a single mouse line, indicating that the development of transgenic lines showing new features of the AD-like brain should be explored. Here we report on a transgenic mouse line, named Tg-APP (Sw, V717F)/B6, that expresses the human amyloid precursor protein (APP) containing the Swedish and the V717F Indiana mutations in the brains of inbred C57BL/6 mice, designed to eliminate the potential phenotypic variations attributed to the compound genetic backgrounds adopted in most AD mouse models. The Tg-APP (Sw, V717F)/B6 mice expressed the transgene transcript, in the heterozygote state, at a level of 2.6 +/- 0.1 fold higher than that of endogenous mouse APP. However, no Abeta-plaque deposition was produced in the brain of the Tg-APP (Sw, V717F)/B6 mice up to 18 months of age. The Tg-APP(Sw, V717F)/B6 mice at 13-15 months showed reduced expression of calbindin and c-Fos in the brain. The Tg-APP (Sw, V717F)/B6 mice at 11-14 months displayed decreased motor coordination, learning and memory deficits, and severely increased anxiety. These phenotypes were not observed in the Tg-APP (Sw, V717F)/B6 mice at 5-7 months. Microarray analysis revealed altered expression, in the amygdala of the Tg-APP (Sw, V717F)/B6 mice, of genes previously implicated in anxiety. Taken together, these results suggest that the transgenic APP, or its derivatives, produces the age-dependent pathophysiology of the AD-like brain and that the progressive cognitive impairment and anxiety induction can proceed in the absence of visible Abeta-plaque deposition. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/15114629/Progressive_cognitive_impairment_and_anxiety_induction_in_the_absence_of_plaque_deposition_in_C57BL/6_inbred_mice_expressing_transgenic_amyloid_precursor_protein_ L2 - https://doi.org/10.1002/jnr.20127 DB - PRIME DP - Unbound Medicine ER -