Taconic Transgenic Exchange

APOE4

HUMANIZED KNOCK IN

Licensing Requirements

C57BL/6 Background

Model Number	Zygosity	Nomenclature
1549-F	Homozygous	B6.129P2-Apoe^{tm3(APOE4)Mae}* N8
1549-M	Homozygous	B6.129P2-Apoe^{tm3(APOE4)Mae}* N8

Model Description

Homozygous for a human APOE4 gene targeted replacement of the endogenous mouse Apoe gene
Expresses human apoliprotein E4 isoform under the control of the murine Apoe regulatory sequences
ApoE is a plasma protein involved in cholesterol transport, with three human isoforms (E2, E3, and E4) that have been associated with atherosclerosis and Alzheimer's Disease (AD)
E4 occurs in approximately 14% of the human population
In humans, the E4 allele is associated with increased plasma cholesterol and a greater risk of coronary artery disease
On a normal diet, this model has normal plasma cholesterol and triglyceride levels, but altered relative quanities of different plasma lipoprotein particles, and delayed clearance of vLDL particles, with only half the clearance rate observed in the APOE3 targeted replacement mice
On a high-fat diet, develops abnormal serum lipid profiles and atherosclerotic plaques that are more severe than the APOE3 model, with twice the cholesterol, ApoE, and ApoB-48 levels and larger plaques than the APOE3 model
Exhibits an increased risk of atherosclerosis compared with wild type and APOE3 targeted replacement mice
Useful for studying the role of human APOE polymorphism in atherosclerosis, lipid metabolism and Alzheimer's disease

Origin: The APOE4 targeted replacement mouse was developed in the laboratory of Nobuya Maeda at the University of North Carolina. The model was created by targeting the murine Apoe gene for replacement with the human APOE4 allele in E14TG2a ES cells and injecting the targeted cells into blastocysts. Resultant chimeras were backcrossed to C57BL/6 for seven generations (N7). Taconic received stock in 2000. The mice were backcrossed once more (N8) and embryo transfer derived. The colony is maintained through mating of homozygotes.

Color: Black

Genetics: Carries Nnt mutation

Initial Publication:

Knouff C, Hinsdale ME, Mezdour H, Altenburg MK, Watanabe M, Quarfordt SH, Sullivan PM, Maeda N. (1999) ApoE structure determines VLDL clearance and atherosclerosis risk in mice. J Clin Invest, 103(11):1579-86.

Animal Diet: NIH #31M Rodent Diet

Licensing Requirements:

Label License: Conditions of Use for Taconic Transgenic Models™
Taconic Transgenic Models (Models) are produced and distributed under rights to patents and intellectual property licensed from various institutions. Taconic sells the Models to purchasers, and grants to each purchaser a right under Taconic's rights in such licensed patents and intellectual property to use the purchased Model in consideration of purchasers' acknowledgement of and agreement to the Terms and Conditions of Sale and the following terms of use:

Title to these Models and biological materials derived from them remains with Taconic Farms, Inc
The Models will be used for research purposes only
The Models will not be bred except to obtain embryos or fetuses required for research purposes
The Models and biological materials derived from them will not be distributed to third parties or used for commercial purposes.

Taconic Transgenic Models are produced in Isolated Barrier Unit (IBU™) facilities under MPF™ conditions, and shipped in Taconic Transit Cages (TTC™).