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| These transgenic mice express the mouse Abca1 (ATP-binding cassette, sub-family A (ABC1), member 1) gene under the control of the mouse Prnp (prion protein) promoter. These founder line E mice have a 6-fold increase in expression of ABCA1 in the cortex over wild-type levels. Transgenic mice exhibit reduced apoE levels in the hippocampus and cerebrospinal fluid (CSF). These mice may be useful in studies of the underlying mechanism of amyloid deposition in the brain and Alzheimers disease. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
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Description
Strain Information
Type Congenic; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Hemizygote x +/+ sibling (Female x Male) 23-JAN-09 Species laboratory mouse Generation N5+F10 (10-AUG-11)
Generation DefinitionsDonating Investigator Dr. David M. Holtzman, Washington University Description
These transgenic mice express the mouse Abca1 (ATP-binding cassette, sub-family A (ABC1), member 1) gene under the control of the mouse Prnp (prion protein) promoter.These founder line E mice have a 6-fold increase in expression of ABCA1 in the cortex over wild-type levels. Trangene expression is high in total brain tissue, kidney, testis and muscle as detected by Western blot analysis. Transgenic mice exhibit reduced apoE levels: 40% of wild-type levels in the hippocampus, approximately half of wild-type levels in cerebrospinal fluid (CSF). The apoE protein that is overexpressed has altered biochemical properties and is not as soluble as that found in controls. Lipoprotein particles from the CSF that contain apoE protein are larger in size than wild-type, indicating that the transgenic apoE particles are more lipidated.
Male transgenic mice have atropied testes, defective spermatogenesis and are infertile. The strain can be maintained by mating hemizygous females to wild-type males.
These mice may be useful in studies of the underlying mechanism of amyloid deposition in the brain and Alzheimers disease.
Development
A transgenic construct containing the mouse Abca1 (ATP-binding cassette, sub-family A (ABC1), member 1) gene under the control of the mouse Prnp (prion protein) promoter was injected into fertilized B6CBAF1 eggs. Founder line E was subsequently established. The mice were backcrossed to C57BL/6 (see SNP notes below) for four generations. After arriving at The Jackson Laboratory, the mice were backcrossed to C57BL/6J for one generation.A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (108 strains)
021067 B6.Cg-Abca1tm1Jp Abcg1tm1Tall/J 003897 DBA/1-Abca1tm1Jdm/J
Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Phenotype
Phenotype Information
- Potential model based on transgenic expression of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. ATP-Binding Cassette, Subfamily A, Member 1; ABCA1 (ABCA1)
Hypercholesterolemia, Familial (ABCA1)
Hypoalphalipoproteinemia, Primary (ABCA1)
Tangier Disease; TGD (ABCA1)
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Prnp-Abca1)EHol/0
involves: C57BL/6 * CBA
- reproductive system phenotype
- abnormal spermatogenesis
- elongated spermatids and spermatozoa are absent in testes of mutant males (MGI Ref ID J:131400)
- abnormal testis morphology
- 3-fold increased numbers of apoptotic cells in testes relative to controls (MGI Ref ID J:131400)
- abnormal testis development
- testes exhibit maturation arrest due to absence of mature products of spermatogenesis (MGI Ref ID J:131400)
- decreased testis weight
- 50% reduction in testes mass relative to wild-type controls (MGI Ref ID J:131400)
- seminiferous tubule degeneration
- tubules display atrophy with marked degenerative changes such as large increase in multinucleated giant cells and cells with condensed nuclei (MGI Ref ID J:131400)
- testicular atrophy
- severe atrophy (MGI Ref ID J:131400)
- male infertility (MGI Ref ID J:131400)
- nervous system phenotype
- abnormal glial cell physiology
- Apoe-containing lipoprotein particles secreted by astrocytes contain more lipid than those secreted by non-transgenic controls; lipoprotein fractions contain a greater ratio of cholesterol to Apoe (MGI Ref ID J:131400)
- amyloid beta deposits
- in 12-month old mice have frequent amyloid beta (Abeta) deposits in cortex and hippocampus including molecular layer of hippocampus (MGI Ref ID J:131400)
- almost no deposits are observed in hilus of dentate gyrus of hippocampus (MGI Ref ID J:131400)
- thioflavin-S positive fibrillar Abeta plaques are frequently observed in cortex and hippocampus at 12 months (MGI Ref ID J:131400)
- thioflavin-S positive plaques are associated with reactive microglia (MGI Ref ID J:131400)
- other phenotype
- amyloid beta deposits
- in 12-month old mice have frequent amyloid beta (Abeta) deposits in cortex and hippocampus including molecular layer of hippocampus (MGI Ref ID J:131400)
- almost no deposits are observed in hilus of dentate gyrus of hippocampus (MGI Ref ID J:131400)
- thioflavin-S positive fibrillar Abeta plaques are frequently observed in cortex and hippocampus at 12 months (MGI Ref ID J:131400)
- thioflavin-S positive plaques are associated with reactive microglia (MGI Ref ID J:131400)
- endocrine/exocrine gland phenotype
- abnormal testis morphology
- 3-fold increased numbers of apoptotic cells in testes relative to controls (MGI Ref ID J:131400)
- abnormal testis development
- testes exhibit maturation arrest due to absence of mature products of spermatogenesis (MGI Ref ID J:131400)
- decreased testis weight
- 50% reduction in testes mass relative to wild-type controls (MGI Ref ID J:131400)
- seminiferous tubule degeneration
- tubules display atrophy with marked degenerative changes such as large increase in multinucleated giant cells and cells with condensed nuclei (MGI Ref ID J:131400)
- testicular atrophy
- severe atrophy (MGI Ref ID J:131400)
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype
- plasma levels of cholesterol including HDL-associated cholesterol and phospolipids, and Apoe are not significantly different from controls at 3 months (MGI Ref ID J:131400)
Neurobiology Research
Alzheimer's Disease
Reproductive Biology Research
Fertility Defects
males only
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(Prnp-Abca1)EHol | ||
|---|---|---|---|
| Allele Name | transgene insertion E, David M Holtzman | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | PrP-mAbca1 line E; | ||
| Mutation Made By | Dr. David Holtzman, Washington University | ||
| Strain of Origin | (C57BL/6 x CBA)F1 | ||
| Expressed Gene | Abca1, ATP-binding cassette, sub-family A (ABC1), member 1, mouse, laboratory | ||
| Promoter | Prnp, prion protein, mouse, laboratory | ||
| Molecular Note | A transgenic construct containing the mouse Abca1 (ATP-binding cassette, sub-family A (ABC1), member 1) gene under the control of the mouse Prnp (prion protein) promoter was injected into fertilized B6CBAF1 eggs. Founder line E was subsequently established. These founder line E mice have a 6-fold increase in expression of ABCA1 in the cortex over wildtype levels. Transgene expression is high in total brain tissue, kidney, testis and muscle as detected by Western blot analysis. [MGI Ref ID J:131400] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Prnp-Abca1), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Wahrle SE; Jiang H; Parsadanian M; Kim J; Li A; Knoten A; Jain S; Hirsch-Reinshagen V; Wellington CL; Bales KR; Paul SM; Holtzman DM. 2008. Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J Clin Invest 118(2):671-82. [PubMed: 18202749] [MGI Ref ID J:131400]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number MGL375
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these transgenic mice can be bred by mating female hemizygote to a wildtype male. Male transgenic mice are sterile. Mating System Hemizygote x +/+ sibling (Female x Male) 23-JAN-09 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Hemizygous for Tg(Prnp-Abca1)EHol
Price per Pair (US dollars $) Pair Genotype $296.00 Hemizygous for Tg(Prnp-Abca1)EHol x Noncarrier Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Hemizygous for Tg(Prnp-Abca1)EHol
Price per Pair (US dollars $) Pair Genotype $384.80 Hemizygous for Tg(Prnp-Abca1)EHol x Noncarrier Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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|
|
Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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