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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. | |||||||||||||||
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+ (22-JAN-09) Donating Investigator David 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 for four generations. After arriving at The Jackson Laboratory, the mice were backcrossed to C57BL/6J for one generation.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Abca1
003897 DBA/1-Abca1tm1Jdm/J View Strains carrying other alleles of Abca1 (1 strain)
Strains carrying other alleles of Prnp
View Strains carrying other alleles of Prnp (20 strains)
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
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 (MGI Ref ID J:131400)
- elongated spermatids and spermatozoa are absent in testes of mutant males
- abnormal testis morphology (MGI Ref ID J:131400)
- 3-fold increased numbers of apoptotic cells in testes relative to controls
- abnormal testis development (MGI Ref ID J:131400)
- testes exhibit maturation arrest due to absence of mature products of spermatogenesis
- decreased testis weight (MGI Ref ID J:131400)
- 50% reduction in testes mass relative to wild-type controls
- seminiferous tubule degeneration (MGI Ref ID J:131400)
- tubules display atrophy with marked degenerative changes such as large increase in multinucleated giant cells and cells with condensed nuclei
- testicular atrophy (MGI Ref ID J:131400)
- severe atrophy
- male infertility (MGI Ref ID J:131400)
- nervous system phenotype
- abnormal glial cell physiology (MGI Ref ID J:131400)
- 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
- amyloid beta deposits (MGI Ref ID J:131400)
- in 12-month old mice have frequent amyloid beta (Abeta) deposits in cortex and hippocampus including molecular layer of hippocampus
- almost no deposits are observed in hilus of dentate gyrus of hippocampus
- thioflavin-S positive fibrillar Abeta plaques are frequently observed in cortex and hippocampus at 12 months
- thioflavin-S positive plaques are associated with reactive microglia
- other phenotype
- amyloid beta deposits (MGI Ref ID J:131400)
- in 12-month old mice have frequent amyloid beta (Abeta) deposits in cortex and hippocampus including molecular layer of hippocampus
- almost no deposits are observed in hilus of dentate gyrus of hippocampus
- thioflavin-S positive fibrillar Abeta plaques are frequently observed in cortex and hippocampus at 12 months
- thioflavin-S positive plaques are associated with reactive microglia
- endocrine/exocrine gland phenotype
- abnormal testis morphology (MGI Ref ID J:131400)
- 3-fold increased numbers of apoptotic cells in testes relative to controls
- abnormal testis development (MGI Ref ID J:131400)
- testes exhibit maturation arrest due to absence of mature products of spermatogenesis
- decreased testis weight (MGI Ref ID J:131400)
- 50% reduction in testes mass relative to wild-type controls
- seminiferous tubule degeneration (MGI Ref ID J:131400)
- tubules display atrophy with marked degenerative changes such as large increase in multinucleated giant cells and cells with condensed nuclei
- testicular atrophy (MGI Ref ID J:131400)
- severe atrophy
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype (MGI Ref ID J:131400)
- plasma levels of cholesterol including HDL-associated cholesterol and phospolipids, and Apoe are not significantly different from controls at 3 months
- abnormal protein level (MGI Ref ID J:131400)
- mice show 40% reduction in Apoe levels in hippocampus at 3 months; in CSF, levels of Apoe are decreased >40%
- brain lysates contain significantly lower levels of Clusterin than control samples
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Neurobiology Research
Alzheimer's Disease
Reproductive Biology Research
Fertility Defects
males only
| 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 | 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 Protocols
Tg(Prnp-Abca1), Standard PCR
Tg(Prnp-Abca1), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
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]
Animal Health Reports
Room Number MGL375/MGL377
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 for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $243.50 Female or Male Hemizygous for Tg(Prnp-Abca1)EHol
Pairs /Price (US dollars $) Pair Genotype $297.85 Hemizygous for Tg(Prnp-Abca1)EHol x Noncarrier
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $316.60 Female or Male Hemizygous for Tg(Prnp-Abca1)EHol
Pairs /Price (US dollars $) Pair Genotype $387.30 Hemizygous for Tg(Prnp-Abca1)EHol x Noncarrier
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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