APOE4

Targeted Replacement

APOE4 Targeted Replacement Mouse Model

C57BL/6NTac Background

  • Model #
  • Genotype
  • Nomenclature
  • 1549-F
    hu/hu
    B6.129P2-Apoetm3(APOE*4)Mae N8
  • 1549-M
    hu/hu
    B6.129P2-Apoetm3(APOE*4)Mae N8
  • Homozygous for a human APOE4 gene targeted replacement of the endogenous mouse Apoe gene
  • Expresses human apolipoprotein 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 quantities 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
Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.

Genetic Background:

C57BL/6NTac background, nearly congenic on C57BL/6NTac background with non-C57BL/6NTac character remaining in a few loci.

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. Additional backcrossing to C57BL/6NTac was completed and the line is nearly congenic on C57BL/6NTac, with a few loci remaining which are not consistent with C57BL/6NTac. The colony is maintained through mating of homozygotes.

Genetics:

Does not carry Nnt mutation

Color:

Black

Species:

Mouse

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.


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, 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 for Taconic Models, Products and Services and the following terms of use:
  • Title to these Models and biological materials derived from them remains with Taconic.
  • The Models will be used for research purposes only.
  • The Models will not be bred or cross-bred except to obtain embryos or fetuses required for research purposes unless additional rights have been granted in writing by Taconic.
  • The Models and biological materials derived from them will not be distributed to third parties or used for commercial purposes.
  • Non-profit purchasers may not use this Model and/or biological materials derived from it in sponsored research or contract research studies unless it is purchased at the for-profit price.
Figure 1: Immunohistochemical analysis of paraffin-embedded liver (left) or brain (right) from wild type C57BL/6NTac females (model #B6-F, top) and APOE4 females (model #1549-F, genotype hu/hu, bottom) mice (model #1549) using using ApoE (pan) (D7I9N) Rabbit mAb #13366 (human-reactive) from Cell Signaling Technology, Inc.

Figure 2: Western blot analysis of extracts from HepG2 cells (lane 1), 293T mock transfected (lane 2) or transiently transfected with a construct expressing ApoE4 (lane 3), whole liver extracts from wild type female C57BL/6NTac mice (model #B6-F, lane 4), or female ApoE4 knock-in (model #1549-F, lane 5), whole brain extracts from wild type female C57BL/6NTac mice (model # B6-F, lane 6), or female ApoE4 knock-in (model # 1549-F, lane 7), using ApoE (pan) (D7I9N) Rabbit mAb #13366 (human-reactive, upper) and β-Actin (D6A8) Rabbit mAb #8457 (lower), both antibodies from from Cell Signaling Technology, Inc.

Figure 3: Immunohistochemical analysis of paraffin-embedded brain from wild type C57BL/6NTac female mice (model #B6-F, top) and APOE4 female mice (model #1549-F, genotype hu/hu, bottom) using ApoE (pan) (E8C2U) Mouse mAb #74417 (human-reactive, left) compared to concentration-matched Mouse (E7Q5L) mAb IgG2b Isotype Control #53484 (right), both antibodies from Cell Signaling Technology, Inc.

Figure 4: Immunohistochemical analysis of paraffin-embedded liver from wild type C57BL/6NTac female mice (model #B6-F, top) and APOE4 female mice (model #1549-F, genotype hu/hu, bottom) using ApoE (pan) (E8C2U) Mouse mAb #74417 (human-reactive, left) compared to concentration-matched Mouse (E7Q5L) mAb IgG2b Isotype Control #53484 (right), both antibodies from Cell Signaling Technology, Inc.

Figure 5: Western blot analysis of extracts from HepG2 cells (lane 1), 293T mock transfected (lane 2) or transiently transfected with a construct expressing ApoE4 (lane 3), whole liver extracts from wild type C57BL/6NTac female mice (model #B6-F, lane 4), or female ApoE4 knock-in mice (model #1549-F, lane 5), whole brain extracts from wild type C57BL/6NTac female mice (model #B6-F, lane 6), or female ApoE4 knock-in mice (model 1549-F, lane 7), using ApoE (E8C2U) Mouse mAb #74417 (human-reactive, upper) and β-Actin (D6A8) Rabbit mAb #8457 (lower), both antibodies from from Cell Signaling Technology, Inc.

Figure 6: Immunohistochemical analysis of paraffin-embedded liver (left) or brain (right) from wild type C57BL/6NTac female mice (model #B6-F, top) and female APOE4 mice (model #1549-F, hu/hu, bottom) using ApoE (E7X2A) Rabbit mAb #49285 (mouse-reactive) from Cell Signaling Technology, Inc.

Figure 7: Western blot analysis of extracts from HepG2 cells (lane 1), 293T mock transfected (lane 2) or transiently transfected with a construct expressing ApoE4 (lane 3), whole liver extracts from wild type C57BL/6NTac female mice (model #B6-F, lane 4), or female ApoE4 knock-in (model #1549-F) (lane 5), whole brain extracts from wild type C57BL/6NTac female mice (model #B6-F, lane 6), or female ApoE4 knock-in mice (model #1549-F) (lane 7), using ApoE (E7X2A) Rabbit mAb #49285 (mouse-reactive, upper) and β-Actin (D6A8) Rabbit mAb #8457 (lower), both antibodies from Cell Signaling Technology, Inc.

Figure 8: Immunohistochemical analysis of paraffin-embedded liver (left) or brain (right) from wild type C57BL/6NTac female mice (model #B6-F, top) and female APOE4 mice (model #1549-F, genotype hu/hu, bottom) using ApoE4 (E5M4L) Rabbit mAb (human-reactive) from Cell Signaling Technology, Inc.

Figure 9: Western blot analysis of extracts from HepG2 cells (lane 1), 293T mock transfected (lane 2) or transiently transfected with a construct expressing ApoE4 (lane 3), whole liver extracts from wild type C57BL/6NTac female mice (model #B6-F, lane 4), or Female ApoE4 knock-in mice (model #1549-F, lane 5), using ApoE4 (E5M4L) Rabbit mAb #39327 (upper) and β-Actin (D6A8) Rabbit mAb #8457 (lower),both antibodies from Cell Signaling Technology, Inc.
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