Updated 20 May 2005

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Name/ Symbol Strain Name Transgene/ Promoter and Regulatory Elements Genetic Background Behavioral  Phenotype Neurological  Characteristics Patents/  Availability Primary Citation ApoE4(Δ272-299) and (Δ241-299) Symbol: ApoE Posted 5/22/05   Human apoE4 (Δ272-299) or (Δ241-299) with a signal peptide for secretion and a FLAG tag at the amino terminus were subcloned into neuron-specific Thy-1.2 vector. Origin C57BL/6J; Backcrossed with ApoE-null mice, N>6 Mice expressing lower levels of apoE4 (D272-299) were viable and fertile. Mice expressing high levels died at 2-4 months of age. Mice express endogenous ApoE. High level expressing ApoE4 (Δ272-299) mice displayed AD-like neurodegenerative alterations in cortex and hippocampus. Low level expressing mice survived longer but showed impaired learning and memory at 6-7 months of age. Patents: US678751982, filing date 11/02/01, issue date 09/07/04 Contact: Yadong Huang Harris et al., 2003 NSE-ApoE4 Symbol: ApoE Posted 5/22/05   ApoE4 minigene (part of exon 1, first intron, first 6 bp of exon 2, third intron of hAPOE gene, hApoE cDNA coding region, and noncoding sequence with arginine at aa 112). Rat NSE promoter. 75% C57BL/6J. Backcrossed with murine apoE-null mice, N>20 NSE-apoE4 mice showed impairments in learning a water maze task and in vertical exploratory behavior that increased with age and were seen primarily in females. Neuronal apoE expression throughout brain. Expression of apoE4 did not protected against excitotoxin (Kainic acid)-induced neuronal. Patents: 6,046,381, filing date 4/30/1998, issue date 4/4/2000 Contact: Dr. Robert W. Mahley Raber et al., 1998 NSE-ApoE3 Symbol: ApoE Posted 5/22/05   The ApoE3 minigene ( part of exon 1, first intron, first 6 bp of exon 2, hApoE cDNA coding region, and noncoding sequence with cysteine at aa112). Rat NSE enolase promoter. 75% C57BL/6J. Backcrossed with murine apoE-null mice, N>20   Neuronal apoE expression throughout brain. Expression of apoE3 protected against excitotoxin (Kainic acid)-induced neuronal damage and against the age-dependent neurodegeneration seen in Apoe-/- mice. Patents: 6,046,381, filing date 4/30/1998, issue date 4/4/2000 Contact: Dr. Robert W. Mahley Raber et al., 1998 ApoE4 (line 3R1) Symbol: ApoE Posted 10/28/04 C3;B6-Tg(Prnp-APOE4) 3Dbo 3-way PCR strategy/ hApoE4/MoPrP.XhoI Origin: C57BL/6J x C3H/HeJ Not assessed. No obvious behavioral features or change in lifespan. High levels hApoE4 in astroglia and neurons. Astroglia secrete ApoE4 at 5x the normal murine ApoE. High levels not associated with neuropathological abnormalities. Under Development UNC MMRRC Stock # 0399-UNC Web site: http://www.mmrrc.org/ Email: MMRRC Lesuisse et al., 2001 ApoE4 KI Symbol: ApoE Posted 10/28/04   The floxed neo cassette on APOE KI mice was removed through cre-mediated loxP excision /replaced mouse Apoe with human APOE4/promoter mouse Apoe Origin: 129P2/OlaHsd (ES cell line E14TG2aIV) Background: C57BL/6J generation N8 N/A Low brain APOE and serum cholesterol levels compared to APOE2 and APOE3 KI mice. APOE4 KI mice x APP B6-R1.40 show higher levels of brain cholesterol relative to non-transgenic animals. Available Bruce Lamb btl@cwru.edu Mann et al., 2004 ApoE3 KI Symbol: ApoE Posted 10/28/04   The floxed neo cassette on APOE KI mice was removed through cre-mediated loxP excision /replaced mouse Apoe with human APOE3/promoter mouse Apoe Origin: 129P2/OlaHsd (ES cell line E14TG2aIV) Background: C57BL/6J generation N8 N/A Intermediate brain APOE and serum cholesterol levels compared to APOE2 and APOE4 KI mice. APOE3 KI mice x APP B6-R1.40 show higher levels of brain cholesterol relative to non-transgenic animals. Available Bruce Lamb btl@cwru.edu Mann et al., 2004 ApoE2 KI Symbol: ApoE Posted 10/26/04   The floxed neo cassette on APOE KI mice was removed through cre-mediated loxP excision /replaced mouse Apoe with human APOE2/promoter mouse Apoe Origin: 129P2/OlaHsd (ES cell line E14TG2aIV) Background: C57BL/6J generation N8 N/A High brain APOE and serum cholesterol levels compared to APOE3 and APOE4 KI mice. APOE2 KI mice x APP B6-R1.40 show higher levels of brain cholesterol relative to non-transgenic animals. The presence of hAPOE increases brain Aβ levels in a genomic-based model of AD, irrespective of genotype. Available Bruce Lamb btl@cwru.edu Mann et al., 2004 ApoE4 Targeted Replacement Mouse (See Taconic datasheet) Symbol: Apoe4 Posted 1/8/2004 M6.129P2-TgHAPOE4N8 hApoE4 construct replaced mouse ApoE/129ES cells. C57BL/6J N8 homozygous matings Mice have normal cholesterol and triglyceride levels but different quantities of lipoprotein particles. human apoE mRNA in the liver, brain, and other tissues is functional Available at Taconic Stock# 001549-M Knouff et al., 1999 ApoE3 Targeted Replacement Mouse (See Taconic datasheet) Symbol: Apoe 3 Posted 1/8/2004 M6.129P2-TgHAPOE3N8 hApoE3 construct replaced mouse ApoE/129ES cells. C57BL/6J N8 homozygous matings On a high fat diet, mice had 5x level of cholesterol compared to control. Arterosclerotic human apoE mRNA found in the liver, brain, and other tissues, is functional. Available at Taconic Stock# 001548-M Sullivan et al., 1997 ApoE4 Updated 1/8/2004   hApoE4/Mouse Thy-1, PDGF, GFAP or mouse (PGK) /FVB/N Origin: C57BL/6 axonal degeneration (Wallerian), muscular degeneration, motoric problems. Premature death in Thy-ApoE4 tg mice. Thy-1-ApoE4 and PDGE-ApoE4 tg mice expressed hApoE4 in neurons resulting in axonopathy in brain and spinal cord and hyperphosphorylation of protein tau. All tg mice express hApoE4 in spinal cord. Unpatented Contact Paul Vandun Tesseur I et al., 2000 ApoE4   human ApoE4 cDNA with C112R mutation and double L28P; C112R mutations/ rat GFAP gene promoter cDNA microinjected into the male pronuclei of B6D2FI zygote, reimplanted into pseudopregnant B6CBAFI females.  No behavioral abnormalities No abnormal pathology Unpatented Huber G et al ApoE tm1 (See Taconic datasheet) Symbol: Apoe Posted 1/8/2004 M6.129P2-Apotm1N11 plasmids (pJPB63 and pNMC109) to knockout Apoe / Thy and/or Neo gene/(E14TG2a) ES cells. 129 and/or C57BL/6J Develop normal and healthy. 5X normal cholesterol, develop artherosclerotic lesions which progress to occlusions of coronary artery by 8 months.   Available at Taconic Stock# APOE-M Piedrahita et al., 1992 Apoe2 Targeted Replacement Mouse (See Taconic datasheet) Symbol:Apoe2 Posted 1/8/2004 M6.129P2-TgHAPOE2N8 hApoE2 construct replaced mouse ApoE/129ES cells. C57BL/6J N8 homozygous matings Mice have characteristics of type III hyperlipoproteinemia, defective in clearing migrating VLDL particles, and spontaneously develop atherosclerotic plaques even on a regular diet.   Available at Taconic Stock# 001547-M Sullivan et al., 1998 ApoE2   hApoE/ PDGF- or TF promoters/ C57BL/6 fertilized oocytes Origin C57BL/6 (Tac), apoE2 tg bred back to ApoE-/-background Tg mice develop normally; show no macroscopic difference compared to their nontg littermates. PDGF tg express ApoE2 in the brain and hippocampal neurons. TF tg mice express ApoE2 in brain, serum, liver and in glial cells. Over expression of ApoE restores the synaptophysin immunoreactivity levels in the brain. Contact: vzannis@bu.edu.. Georgopoulos et al., 2002 C57BL/6J-ApoEtm1Unc or B6.129P2-Apoetm1Unc (See JAX datasheet) Symbol: Apoe Posted 11/25/2003 B6.129P2-Apoetm1Unc/J Plasmid pNMC109 disrupted ApoE gene, electroporated into E14TG2a (129) ES cells. Backcross C57BL/6, generation N12, mate Homozygote x Homozygote   APOE deficient mice have altered responses to stress, impaired spatial learning and memory, altered long term potentiation, and synaptic damage. Available The Jackson Lab: Stock 002052 Piedrahita et al. 1992 GFAP-ApoE2 line14 (See JAX datasheet) Symbol: APOE2 Updated 1/18/05 B6.Cg-Tg(GFAP-APOE2) 14HolApoetm1Unc/J hApoE3 isoform/h GFAP promoter/ B6;CBA donor eggs. backcross B6.129P2-Apoetm1Unc (Stock #: 2052) for six generations. Mice are viable, normal in size and do not display any gross physical or behavioral abnormalities. Only hApoE2 expressed, detected in glia and neuropil in developing and adult mutant mice. Available The Jackson Lab: Stock 004632 Sun et al. 1998 GFAP-ApoE3 line 37 (See JAX datasheet) Symbol: APOE3 Updated 1/18/05 B6.Cg-Tg(GFAP-APOE3) 37HolApoetm1Unc/J hApoE3 isoform/h GFAP promoter/ B6;CBA donor eggs. The resulting transgenic founder animals were bred to B6.129P2-Apoetm1Unc (Stock #: 2052) for ten generations. Mice are viable, normal in size and do not display any gross physical or behavioral abnormalities. Only hApoE3 expressed, detected in glia and neuropil in developing and adult mutant mice. Available The Jackson Lab: Stock 004633 Sun et al. 1998 GFAP-ApoE4 line 1 (See JAX datasheet) Symbol: APOE4 Updated 1/18/05 B6.Cg-Tg(GFAP-APOE4) 1Hol Apoetm1Unc/J hApoE4 isoform/h GFAP promoter/ B6;CBA donor eggs. Backcross B6.129P2-Apoetm1Unc (Stock #: 2052) for six generations. Mice are viable, normal in size and do not display any gross physical or behavioral abnormalities. Only hApoE4 expressed, detected in glia and neuropil in developing and adult mutant mice. Available The Jackson Lab: Stock 004631 Sun et al. 1998 Hypomorphic Arg61 ApoE4   Substitute Arg for Thr61. Chimeric mice harboring a mutant Apoe allele, Apoeneo+, in which intron 3 contained a neo cassette flanked by loxP sites. C57BL/6 HypoE mice were susceptible to diet-induced hypercholesterolemia, but easily reversible. Arg61 Tg expresses only about 5% of normal ApoE mRNA and 2-5% ApoE plasma protein. Unpatented Raffai et al., 2001