These transgenic mice express the human apolipoprotein E4 isoform (APOE4) under the direction of the human glial fibrillary acidic protein (GFAP) promoter and do not express endogenous mouse apolipoprotein E (APOE). Human APOE4 is detectable in glia and neuropil in developing and adult mutant mice. This mutant mouse strain represents a model that may be useful in studies examining the function of APOE4 in the central nervous system and how APOE4 may contribute to the pathology of Alzheimer's disease.
Dr. David M. Holtzman, Washington University
These transgenic mice express the human apolipoprotein E4 isoform (APOE4) under the direction of the human glial fibrillary acidic protein (GFAP) promoter and do not express endogenous mouse apolipoprotein E (Apoe). The transgenic isoform expression pattern follows the endogenous mouse Apoe and GFAP expression patterns in the brain. Human APOE4 is immunodetectable in glia and neuropil in developing and adult mutant mice. Cultured astrocytes from transgenic mice secrete APOE4 in lipoproteins that are similar in size to high-density (HDL) plasma lipoproteins. Detergent-soluble APOE4 protein levels in hemizygous mice forebrain tissue and in adult human cortex tissue are similar. Mice that are hemizygous or homozygous for the transgenic insert and homozygous for the targeted allele are viable, normal in size and do not display any gross physical or behavioral abnormalities. This mutant mouse strain represents a model that may be useful in studies examining the function of APOE4 in the central nervous system and how APOE4 may contribute to the pathology of Alzheimer's disease.
According to the donating investigator, mice that are hemizygous for the transgene and homozygous for the null mutation show dyslipidemia similar to non-transgenic Apoe-null mutant mice (B6.129P2-Apoe
A transgenic construct containing sequence encoding human apolipoprotein E4 isoform under the control of the human glial fibrillary acidic protein (GFAP) promoter was introduced into B6;CBA donor eggs.
|Expressed Gene||APOE, apolipoprotein E, human|
|Site of Expression|
|Allele Name||targeted mutation 1, University of North Carolina|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||APOE KO; AopE(-); ApoE-KO; Apoetm1Un; EKO; apoE-; apoE0; epsilon-; mE-; mEKO|
|Gene Symbol and Name||Apoe, apolipoprotein E|
|Gene Synonym(s)||AD2; AI255918; APO-E; APOEA; ApoE4; LDLCQ5; LPG; expressed sequence AI255918|
|Strain of Origin||129P2/OlaHsd|
|General Note||Phenotypic Similarity to Human Syndrome: Coronary Artery Disease (CAD) in mice homozygous for Apoe tm1Unc and Scarb1 tm1Kri on a mixed 129, BALB/c and C57BL/6 background (J:201999) |
Phenotypic Similarity to Human Syndrome: Metabolic Syndrome in mice homozygous for Apoetm1Unc and Cyp19a1tm1Esi (J:184647)
Phenotypic Similarity to Human Syndrome: Metabolic Syndrome in mice homozygous for Apoetm1Unc and heterozygous for Ay and a (J:177084)
|Molecular Note||Insertion of a neomycin resistance cassette deleted part of exon 3 and part of intron 3 of the Apoe gene. Plasma from homozygous mutant mice gave no detectable immunoprecipitate by the Ouchterlony double immunodiffusion test using a rabbit antibody to rat APOE.|
|Mutations Made By|| |
Dr. Nobuyo Maeda, University of North Carolina at Chapel Hill
|Allele Name||transgene insertion 1, David M Holtzman|
|Allele Type||Transgenic (Humanized sequence, Inserted expressed sequence)|
|Allele Synonym(s)||GFAP-apoE4 line1; Tg(GFAP-APOE*4)1Hol; Tg(GFAP-APOE4)1Hol|
|Gene Symbol and Name||Tg(GFAP-APOE_i4)1Hol, transgene insertion 1, David M Holtzman|
|Gene Synonym(s)||GFAP-apoE4 line1; Tg(GFAP-APOE*4)1Hol; Tg(GFAP-APOE*4)1Hol; Tg(GFAP-APOE4)1Hol; Tg(GFAP-APOE4)1Hol|
|Promoter||GFAP, glial fibrillary acidic protein, human|
|Expressed Gene||APOE, apolipoprotein E, human|
|Strain of Origin||C57BL/6 and CBA|
|Molecular Note||The transgene contains sequence encoding human apolipoprotein E4 isoform under the control of the human glial fibrillary acidic protein (GFAP) promoter. Five lines were created (lines 1, 3, 11, 19 and 22) with line 1 being chosen as the representative line based on submission to the Jax repository. The pattern of expression of the human apolipoprotein E3 isoform (APOE3) transgenic product in these mice follows the endogenous mouse APOE and GFAP expression patterns in the brain. Human APOE3 is immunodetectable in glia and neuropil in developing and adult mutant mice.|
|Mutations Made By|| |
Dr. David Holtzman, Washington University
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.