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| IJCEP Copyright © 2007-All rights reserved. |
| International Journal of Clinical and Experimental Pathology |
Int J Clin Exp Pathol 1(2):157-168;2008
Original Article
Seizure Susceptibility and Mortality in Mice that Over-Express Amyloid Precursor
Protein
Cara J. Westmark, Pamela R. Westmark, Ashley M. Beard, Sharon M. Hildebrandt and James S. Malter
Department of Pathology & Laboratory Medicine, Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI
53705
Received 16 July 2007; accepted and available online 1 January 2008
Abstract: Alzheimer’s disease and Fragile X syndrome both display synaptic phenotypes, and based on recent studies, likely share
dendritic over expression of amyloid precursor protein (APP) and β-amyloid (Aβ). In order to create a mouse model to specifically study the
effects of APP and Aβ at synapses, we crossed Tg2576, which over-express human APP with the Swedish mutation (hAPPsw), with fmr-1
KO mice. The progeny, named FRAXAD, displayed increased mortality (23% by 30 days of age) compared to Tg2576 (3%) and WT and
fmr-1 KO littermate controls (0%) consistent with a developmental defect. By 60 days of age, both the Tg2576 and FRAXAD mice
approached a 40% mortality rate compared to 0% for WT and fmr-1 KO littermates. To understand the mechanism underlying increased
mortality in APP over-expressing mice, we assessed seizure thresholds in response to pentylenetetrazol (PTZ). Both the Tg2576 and
FRAXAD mice had a lower threshold to PTZ-induced seizures (average seizure score of ≥4.0) in comparison to non-transgenic littermates
(average seizure score 1.9-2.9). Seizures are a major phenotype of AD, FXS, Down syndrome, autism and epilepsy, and these data
suggested that developmental over-expression of dendritic APP or Aβ increased seizure susceptibility. (IJCEP707007).
Key Words: amyloid, amyloid precursor protein, Fragile X mental retardation protein, FRAXAD, seizure, synapse
Full Text PDF
Supplementary data: Supplementary figures & Table , video 1, video 2, video 3, video 4 and video 5.
Address all correspondences to: Dr. Cara J. Westmark, Department of Pathology & Laboratory Medicine, Waisman Center for
Developmental Disabilities, University of Wisconsin, Madison, WI 53705. Email: westmark@facstaff.wisc.edu
Original Article
Seizure Susceptibility and Mortality in Mice that Over-Express Amyloid Precursor
Protein
Cara J. Westmark, Pamela R. Westmark, Ashley M. Beard, Sharon M. Hildebrandt and James S. Malter
Department of Pathology & Laboratory Medicine, Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI
53705
Received 16 July 2007; accepted and available online 1 January 2008
Abstract: Alzheimer’s disease and Fragile X syndrome both display synaptic phenotypes, and based on recent studies, likely share
dendritic over expression of amyloid precursor protein (APP) and β-amyloid (Aβ). In order to create a mouse model to specifically study the
effects of APP and Aβ at synapses, we crossed Tg2576, which over-express human APP with the Swedish mutation (hAPPsw), with fmr-1
KO mice. The progeny, named FRAXAD, displayed increased mortality (23% by 30 days of age) compared to Tg2576 (3%) and WT and
fmr-1 KO littermate controls (0%) consistent with a developmental defect. By 60 days of age, both the Tg2576 and FRAXAD mice
approached a 40% mortality rate compared to 0% for WT and fmr-1 KO littermates. To understand the mechanism underlying increased
mortality in APP over-expressing mice, we assessed seizure thresholds in response to pentylenetetrazol (PTZ). Both the Tg2576 and
FRAXAD mice had a lower threshold to PTZ-induced seizures (average seizure score of ≥4.0) in comparison to non-transgenic littermates
(average seizure score 1.9-2.9). Seizures are a major phenotype of AD, FXS, Down syndrome, autism and epilepsy, and these data
suggested that developmental over-expression of dendritic APP or Aβ increased seizure susceptibility. (IJCEP707007).
Key Words: amyloid, amyloid precursor protein, Fragile X mental retardation protein, FRAXAD, seizure, synapse
Full Text PDF
Supplementary data: Supplementary figures & Table , video 1, video 2, video 3, video 4 and video 5.
Address all correspondences to: Dr. Cara J. Westmark, Department of Pathology & Laboratory Medicine, Waisman Center for
Developmental Disabilities, University of Wisconsin, Madison, WI 53705. Email: westmark@facstaff.wisc.edu