Posted 22 May 2005

General Information

Transgene: PCR products encoding human apoE4 (Δ272-299) or apoE4 (Δ241-299), both with a signal peptide for secretion and a FLAG tag at the amino terminus, were subcloned into a Thy-1.2 vector. Transgenic mice expressing apoE4 (Δ272-299) or apoE4 (Δ241-299) were generated by microinjecting these DNA constructs into C57BL/6J mouse eggs. All hemizygous transgenic mice were on a pure C57BL/6J background and still expressed endogenous mouse apoE.

Promoter: Neuron-specific Thy-1.2

Mouse strain: Origin: C57BL/6J; Backcrossed with murine apoE-null mice, N>6

Phenotype

Neuropathological analysis

Mice still expressed endogenous mouse apoE. Transgenic mice expressing the carboxyl-terminal-cleaved product, apoE4 (Δ272-299), at high levels in the brain died at 2-4 months of age. The cortex and hippocampus of these mice displayed AD-like neurodegenerative alterations, including abnormally phosphorylated tau (p-tau) and Gallyas silver-positive neurons that contained cytosolic straight filaments with diameters of 15-20 nm, resembling preneurofibrillary tangles. Transgenic mice expressing lower levels of the truncated apoE4 survived longer but showed impaired learning and memory at 6-7 months of age.

Behavioral

Transgenic mice expressing lower levels of apoE4 (Δ272-299) were viable and fertile.

Availability

Licensing/academic distribution contact information:

Yadong Huang
Gladstone Institute of Neurological Disease
1650 Owens Street
San Francisco, CA 94158
Phone: 415-734-2511
Fax: 415-355-0824
Email: yhuang@gladstone.ucsf.edu

Patents: Patent Number: US678751982; Title: Methods of Treating disorders Related to ApoE; Inventors: UCSF/Huang, Y. and Mahley, R.W.; Filing Date: 11/02/2001; Issue Date: 09/07/2004

References

Primary:

Harris F M, Brecht W J, Xu O, Tesseur I , Kekonius L , Wyss-Coray T , Fish J D, Masliah E , Hopkins P C , Scearce-Levie K , Weisgraber K H, Mucke L , Mahley R W and Huang Y. Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice. Proc Natl Acad Sci. 100: 10966-10971, 2003 Abstract.