| 
| ||||||||||||||
| These Abcg5-mutant mice harbor an IRES-LacZ-PGKneo disruption of the adenosine triphosphate-binding cassette (ABC) half-transporter G5 (Abcg5) locus and may be useful in studying sitosterolemia and macrothrombocytopenia, absorption/secretion of plant sterols and cholesterol (hepatic and intestinal), megakaryocyte development, and the relationship between hematological dysfunction and disturbed sterol metabolism. | |||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Donating Investigator Shailendra B Patel, Medical College of Wisconsin Description
Mice homozygous for this adenosine triphosphate-binding cassette (ABC) half-transporter G5 mutant allele (Abcg5-/-) are viable and severely subfertile; the donating investigator reports that males have significantly reduced fertility and females are almost non-fertile. No gene product (mRNA) from the mutant allele is detected in homozygous liver extracts. The expression of beta-galactosidase (lacZ) from the targeted gene is not characterized to date (July 2008). Abcg5-deficient mice exhibit sitosterolemia (high plasma plant sterol concentrations) and macrothrombocytopenia (enlarged platelets caused by defective megakaryocyte development) associated with a near 70% reduction in total number of platelets. Specifically, when allowed ad libitum access to PicoLab Rodent Diet 5053 chow, homozygous mice exhibit strongly elevated plasma levels of β-sitosterol (37-fold) and campesterol (7.7-fold); with further increased levels upon addition of the synthetic Liver-X Receptor agonist T0901317. Homozygotes also exhibit reduced plasma cholesterol concentrations, reduced hepatic expression of the closely related ABC half-transporter G8 (Abcg8), and normal cholesterol secretion into the bile. These Abcg5-mutant mice may be useful in studying sitosterolemia and macrothrombocytopenia, absorption / secretion of plant sterols and cholesterol (hepatic and intestinal), megakaryocyte development, and the relationship between hematological dysfunction and disturbed sterol metabolism.Of note, These Abcg5-mutant mice may also be used in conjunction with other ABC sub-family G mutant strains including G5G8 double mutant mice (Stock No. 004670) and mice bearing a human ABCG5/ABCG8 transgene (Stock No. 004583).
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these Abcg5-mutant mice could vary from that originally described. We will modify the strain description if necessary as published results become available.
Development
A targeting vector was designed to replace an 87-bp fragment corresponding to a segment of exon 3 (encoding the 29 amino acids region containing the conserved adenosine triphosphate-binding cassette signature motifs located in the N-terminal region of the protein) of the targeted gene with an internal ribosomal entry site, beta-galactosidase (lacZ) cDNA, PGK-neomycin resistance cassette, and polyA sequence. This construct was electroporated into "129/OlaHsd"-derived embryonic stem (ES) cells and chimeric mice were used for generation of mutant animals on a "C57BL/6Jx129/OlaHsd" genetic background. These Abcg5-mutant mice were then backcrossed to C57BL/6J inbred mice for at least 10 generations prior to arrival at The Jackson Laboratory. Upon arrival at The Jackson Laboratory, these mice may have been bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Abcg5
001830 A/J-Abcg5trac/J 004670 B6;129S6-Abcg5/Abcg8tm1Hobb/J 004171 CByJ.A-Abcg5trac/J View Strains carrying other alleles of Abcg5 (3 strains)
Phenotype
Phenotype Information
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Sitosterolemia
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Abcg5tm1Plo/Abcg5tm1Plo
involves: 129P2/OlaHsd * C57BL/6J
- homeostasis/metabolism phenotype
- abnormal metabolism
- retention of orally administered radiolabeled beta-sitosterol is increased in the small intestine, liver, and plasma 24 hours after administration (MGI Ref ID J:87209)
- abnormal phospholipid level
- phospholipid concentration in the gallbladder bile is decreased, however the cholesterol/phospholipid ratio is unchanged (MGI Ref ID J:87209)
- decreased cholesterol level
- cholesterol content is reduced in gallbladder bile (MGI Ref ID J:87209)
- decreased circulating cholesterol level
- 60% that of controls (MGI Ref ID J:87209)
- increased circulating plant sterol concentration
- 37- and 7.7-fold increase of the plant sterols beta-sitosterol and campesterol , respectively, in the plasma relative to controls (MGI Ref ID J:87209)
- plasma levels of the plant sterols stigmasterol and brassicasterol are increased (MGI Ref ID J:87209)
- plasma plant sterol concentrations are further elevated when treated with the synthetic LXR agonist T0901317 unlike in wild-type where they are lowered (MGI Ref ID J:87209)
- increased circulating triglyceride level
- plasma triglycerides are elevated, predominantly in the very-low-density lipoprotein-sized lipoprotein fractions (MGI Ref ID J:87209)
- increased circulating VLDL triglyceride level (MGI Ref ID J:87209)
- liver/biliary system phenotype
- abnormal liver physiology
- enlarged liver
- liver is slightly increased in size compared to wild-type (MGI Ref ID J:87209)
Abcg5tm1Plo/Abcg5tm1Plo
involves: 129P2/OlaHsd
- homeostasis/metabolism phenotype
- abnormal lipid homeostasis
- abnormal cholesterol homeostasis
- expression of cholesterol metabolism genes in the liver is altered (MGI Ref ID J:112995)
- liver/biliary system phenotype
- abnormal bile secretion
- basal biliary sterol secretion rates are decreased by 82% (MGI Ref ID J:112995)
- basal biliary phospholipid secretion rates are decreased by 35% (MGI Ref ID J:112995)
- exhibit increased bile flow after the creation of a gallbladder fistula, however bile salt output rates and biliary bile salt composition are unaffected (MGI Ref ID J:112995)
- abnormal liver physiology
- increased liver weight
- liver weights are slightly increased, however this is not due to steatosis as triglyceride levels are not increased (MGI Ref ID J:112995)
This mouse can be used to support research in many areas including:
Cardiovascular Research
Hypercholesterolemia
Hypocholesterolemia
Metabolic Syndrome
Other
altered fat metabolism
altered lipoprotein profile
Vascular Defects
platelet defect
Hematological Research
Platelet Defects
thrombocytopenia
Internal/Organ Research
Liver Defects
Metabolism Research
Lipid Metabolism
Reproductive Biology Research
Fertility Defects
Research Tools
lacZ Expression
Cardiovascular Research
Diabetes and Obesity Research
lacZ
Internal/Organ Research
Metabolism Research
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Abcg5tm1Plo | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Torsten Ploesch | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Abcg5-; | ||
| Mutation Made By | Shailendra Patel, Medical College of Wisconsin | ||
| Strain of Origin | 129P2/OlaHsd | ||
| Site of Expression | Expression of lacZ has not been characterized (July, 2008) | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| Molecular Note | The endogenous locus was disrupted by the insertion of a cassette containing beta galactosidase and neo into exon 3. The insertion deleted 87 bp. [MGI Ref ID J:87209] | ||
| Gene Symbol and Name | Abcg5, ATP-binding cassette, sub-family G (WHITE), member 5 | ||
| Chromosome | 17 | ||
| Gene Common Name(s) | AW112016; STSL; Sterolin-1; cmp; expressed sequence AW112016; tac; thrombocytopenia and cardiomyopathy; trac; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Abcg5tm1Plo, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Plosch T; Bloks VW; Terasawa Y; Berdy S; Siegler K; Van Der Sluijs F; Kema IP; Groen AK; Shan B; Kuipers F; Schwartz M. 2004. Sitosterolemia in ABC-Transporter G5-deficient mice is aggravated on activation of the liver-X receptor. Gastroenterology 126(1):290-300. [PubMed: 14699507] [MGI Ref ID J:87209]
Additional References
Abcg5tm1Plo relatedBrufau G; Kuipers F; Lin Y; Trautwein EA; Groen AK. 2011. A reappraisal of the mechanism by which plant sterols promote neutral sterol loss in mice. PLoS One 6(6):e21576. [PubMed: 21738715] [MGI Ref ID J:174764]
Kruit JK; Drayer AL; Bloks VW; Blom N; Olthof SG; Sauer PJ; de Haan G; Kema IP; Vellenga E; Kuipers F. 2008. Plant sterols cause macrothrombocytopenia in a mouse model of sitosterolemia. J Biol Chem 283(10):6281-7. [PubMed: 18156627] [MGI Ref ID J:133685]
Plosch T; Kruit JK; Bloks VW; Huijkman NC; Havinga R; Duchateau GS; Lin Y; Kuipers F. 2006. Reduction of cholesterol absorption by dietary plant sterols and stanols in mice is independent of the Abcg5/8 transporter. J Nutr 136(8):2135-40. [PubMed: 16857831] [MGI Ref ID J:114929]
Plosch T; van der Veen JN; Havinga R; Huijkman NC; Bloks VW; Kuipers F. 2006. Abcg5/Abcg8-independent pathways contribute to hepatobiliary cholesterol secretion in mice. Am J Physiol Gastrointest Liver Physiol 291(3):G414-23. [PubMed: 16614371] [MGI Ref ID J:112995]
Solca C; Tint GS; Patel SB. 2013. Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice. J Lipid Res 54(2):397-409. [PubMed: 23180829] [MGI Ref ID J:192806]
van der Veen JN; van Dijk TH; Vrins CL; van Meer H; Havinga R; Bijsterveld K; Tietge UJ; Groen AK; Kuipers F. 2009. Activation of the liver X receptor stimulates trans-intestinal excretion of plasma cholesterol. J Biol Chem 284(29):19211-9. [PubMed: 19416968] [MGI Ref ID J:152280]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J (Stock No. 000664) inbred mice. The donating investigator reports that homozygous males have significantly reduced fertility, homozygous females are almost non-fertile, and that fertility can be restored if mice are fed a low plant sterol diet supplemented with the anti-hyperlipidemic drug Ezetimibe.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2574.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
|
|
|
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Payment Terms and Conditions
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
See Terms of Use tab for General Terms and Conditions
The Jackson Laboratory's Genotype Promise
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form
Terms of Use
Terms of Use
General Terms and Conditions
Contact information
General inquiries regarding Terms of UseContracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice, Products & Services Conditions of Use
"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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
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 mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.
No Liability
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 and PRODUCTS 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.