Research Models
PDGF-APPSw,Ind (line J9)
Synonyms: APP(Swedish,Indiana), line J9, hAPPJ9, hAPPlow
Species: Mouse
Genes: APP
Mutations: APP K670_M671delinsNL (Swedish), APP V717F (Indiana)
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: C57BL/6
Availability: Available through Lennart Mucke
Summary
Like the J20 mice, these mice over-express human APP with the Swedish and Indiana mutations. Transgene expression level is relatively low in J9 mice, approximately half the expression seen in J20 mice. Compared with J20 mice, J9 mice develop amyloid plaques more slowly. About 20 percent of J9 mice have plaques at five to seven months, 50 percent at eight to ten months, and 100 percent by 21-25 months (Mucke et al., 2000). J9 mice have also been compared with H6 mice, which overexpress human APP with the Indiana mutation alone. H6 mice have a high level of transgene expression, but less hippocampal Aβ than J9 mice (Hsia et al., 1999).
Because biochemical and functional deficits in J9 mice are rather subtle at baseline, this line is ideal for the assessment of other stressors expected to synergize with Aβ or to increase neuronal susceptibility to the effects of Aβ oligomers.
Neuropathology
Amyloid plaques at eight to ten months, but not at two to four months when deficits in synaptic transmission are observed (Hsia et al., 1999). Approximately 20 percent of mice had plaques at five to seven months, 50 percent at eight to ten months, and 100 percent by 21 to 25 months (Mucke et al., 2000).
Cognition/Behavior
Unknown.
Other Phenotypes
Deficits in synaptic transmission at two to four months, which is prior to amyloid deposition (Hsia et al., 1999).
Modification Details
Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter.
Availability
Available through Lennart Mucke.
Last Updated: 06 Mar 2018
References
Research Models Citations
Paper Citations
- 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 Jun 1;20(11):4050-8. PubMed.
- Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, Kholodenko D, Malenka RC, Nicoll RA, Mucke L. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3228-33. PubMed.
Other Citations
Further Reading
Papers
- Masliah E, Rockenstein E, Veinbergs I, Sagara Y, Mallory M, Hashimoto M, Mucke L. beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12245-50. Epub 2001 Sep 25 PubMed.
- Buttini M, Yu GQ, Shockley K, Huang Y, Jones B, Masliah E, Mallory M, Yeo T, Longo FM, Mucke L. Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid beta peptides but not on plaque formation. J Neurosci. 2002 Dec 15;22(24):10539-48. PubMed.
- 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. PubMed.
- Chin J, Palop JJ, Puoliväli 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. PubMed.
- Roberson ED, Halabisky B, Yoo JW, Yao J, Chin J, Yan F, Wu T, Hamto P, Devidze N, Yu GQ, Palop JJ, Noebels JL, Mucke L. Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease. J Neurosci. 2011 Jan 12;31(2):700-11. PubMed.
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