Updated 2 December 2008

General Information

Transgene: Tg construct: hAPPSwInd. The Swedish mutation was introduced into the PDGF-APPInd transgene (Games, 1995) by PCR primer modification.

Mutation: Swedish (K670N/M671L) and Indiana (V717F)

Promoter: PDGFβ

Mouse strain: B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2J

Neuropathological analysis

-Total Aβ and Aβ1-42 overexpression in neocortical and hippocampus.
-High levels of Aβ (1-42) resulted in age-dependent formation of Aβ plaques in mutant hAPP mice but not wild-type hAPP mice.
-Diffuse Aβ peptides deposition in the dendate gyrus and neocortex forms at 5-7 months
-Amyloid deposition is progressive with all transgenic mice exhibiting plaques by age 8 to 10 months.

Behavioral

WM spatial memory retention, acquisition, deficits 6-7 months (Palop et al., 2003).

Availability

The Jackson Lab
Stock# 004661 extinct;
replaced by Stock# 006293. See TJL datasheet.
Patents: none

References

Primary:

Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci. 2000; 20(11):4050-8. Abstract.

Associated:

Chin J, Palop JJ, Puolivali J, Massaro C, Bien-Ly N, Gerstein H, Scearce-Levie K, Masliah E, Mucke L. Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer's disease. J Neurosci. 2005 Oct 19;25(42):9694-703. Abstract.

Palop JJ, Chin J, Bien-Ly N, Massaro C, Yeung BZ, Yu GQ, Mucke L. Vulnerability of Dentate Granule Cells to Disruption of Arc Expression in Human Amyloid Precursor Protein Transgenic Mice. J. Neurosci., 2005; 25: 9686 - 9693. Abstract.

Aucoin JS, Jiang P, Aznavour N, Tong XK, Buttini M, Descarries L, Hamel E. 2005. Selective cholinergic denervation, independent from oxidative stress, in a mouse model of Alzheimer's disease. Neuroscience 132 :73-86. Abstract.

Patel NV, Gordon MN, Connor KE, Good RA, Engelman RW, Mason J, Morgan DG, Morgan TE, Finch CE. Caloric restriction attenuates Abeta-deposition in Alzheimer transgenic models. Neurobiol Aging. 2005 Jul;26(7):995-1000. Abstract.

Chin J, Palop JJ, Yu GQ, Kojima N, Masliah E, Mucke L. Fyn kinase modulates synaptotoxicity, but not aberrant sprouting, in human amyloid precursor protein transgenic mice. J Neurosci. 2004 May 12;24(19):4692-7. Abstract.

Moolman DL, Vitolo OV, Vonsattel JP, Shelanski ML. Dendrite and dendritic spine alterations in Alzheimer models. J Neurocytol. 2004 May;33(3):377-87. Abstract.

Seabrook TJ, Bloom JK, Iglesias M, Spooner ET, Walsh DM, Lemere CA. Species-specific immune response to immunization with human versus rodent A beta peptide. Neurobiol Aging. 2004 Oct;25(9):1141-51. Abstract.

Palop JJ, Jones B, Kekonius L, Chin J, Yu G-Q, Raber J, Masliah E, Mucke L (2003) Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Proc Natl Acad Sci USA 100: 9572-9577. Abstract.