Description

Strain Information

Former Names B6;129S6-Abcg5/Abcg8tm1Hobb    (Changed: 15-DEC-04 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation F?+2+F1p   Donating Investigator Helen Hobbs,   UT Southwestern Medical Center

Description
Mice that are homozygous for this targeted allele are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected in liver or jejunum. A 2 to 3 fold increase in fractional absorption of dietary plant sterols results in plasma sitosterol levels that are elevated 30 fold compared to wildtype levels. Biliary cholesterol levels are low, as are plasma and liver cholesterol levels. Plasma and liver cholesterol levels increase rapidly (2.4 and 18 fold, respectively) following cholesterol feeding. This mutant mouse strain represents a model that may be useful in studies related to sitosterolemia and cholesterol homeostasis.

Development
The mouse Abcg5 and Abcg8 genes lie in a head-to-head configuration, separated by approximately 400 bp. A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt Abcg5 exons 1 - 2, Abcg8 exons 1 - 3 and the sequence that lies between the two genes. The neomycin resistance gene is flanked by both loxP and FRT (FLP recombinase target sequence) sites. The construct was electroporated into 129S6/SvEv-derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric mice were bred by the Donating Investigator to C57BL/6J once before making the line homozygous.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Abcg5/Abcg8^tm1Hobb/Abcg5/Abcg8^tm1Hobb

        involves: 129S6/SvEvTac * C57BL/6

• digestive/alimentary phenotype
• abnormal lipid absorption (MGI Ref ID J:80679)
  • 2- to 3- fold increase in the fractional absorption of dietary plant sterols
  • the fractional absorption of dietary cholesterol was not significantly different
• homeostasis/metabolism phenotype
• abnormal cholesterol homeostasis (MGI Ref ID J:80679)
  • the cholesterol synthesis rate was significantly lower in the adrenal gland of the female mutant mice
• abnormal circulating cholesterol level (MGI Ref ID J:80679)
  • on 2% cholesterol diet, plasma and liver cholesterol levels increased significantly more than the increase in the wild-type
• decreased circulating cholesterol level (MGI Ref ID J:80679)
  • the plasma and liver cholesterol level were significantly lower than controls on normal diet
• abnormal circulating lipid level (MGI Ref ID J:80679)
  • approximately 30-fold increase in plasma sitosterol
• abnormal circulating cholesterol level (MGI Ref ID J:80679)
  • on 2% cholesterol diet, plasma and liver cholesterol levels increased significantly more than the increase in the wild-type
• decreased circulating cholesterol level (MGI Ref ID J:80679)
  • the plasma and liver cholesterol level were significantly lower than controls on normal diet
• abnormal lipid absorption (MGI Ref ID J:80679)
  • 2- to 3- fold increase in the fractional absorption of dietary plant sterols
  • the fractional absorption of dietary cholesterol was not significantly different
• liver/biliary system phenotype
• abnormal bile composition (MGI Ref ID J:80679)
  • bilary cholesterol concentrations were extremely low

Abcg5/Abcg8^tm1Hobb/Abcg5/Abcg8^tm1Hobb

        involves: 129S6/SvEvTac * C57BL/6

• digestive/alimentary phenotype
• abnormal lipid absorption (MGI Ref ID J:80679)
  • 2- to 3- fold increase in the fractional absorption of dietary plant sterols
  • the fractional absorption of dietary cholesterol was not significantly different
• homeostasis/metabolism phenotype
• abnormal cholesterol homeostasis (MGI Ref ID J:80679)
  • the cholesterol synthesis rate was significantly lower in the adrenal gland of the female mutant mice
• abnormal circulating cholesterol level (MGI Ref ID J:80679)
  • on 2% cholesterol diet, plasma and liver cholesterol levels increased significantly more than the increase in the wild-type
• decreased circulating cholesterol level (MGI Ref ID J:80679)
  • the plasma and liver cholesterol level were significantly lower than controls on normal diet
• abnormal circulating lipid level (MGI Ref ID J:80679)
  • approximately 30-fold increase in plasma sitosterol
• abnormal circulating cholesterol level (MGI Ref ID J:80679)
  • on 2% cholesterol diet, plasma and liver cholesterol levels increased significantly more than the increase in the wild-type
• decreased circulating cholesterol level (MGI Ref ID J:80679)
  • the plasma and liver cholesterol level were significantly lower than controls on normal diet
• abnormal lipid absorption (MGI Ref ID J:80679)
  • 2- to 3- fold increase in the fractional absorption of dietary plant sterols
  • the fractional absorption of dietary cholesterol was not significantly different
• liver/biliary system phenotype
• abnormal bile composition (MGI Ref ID J:80679)
  • bilary cholesterol concentrations were extremely low

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cardiovascular Research
Hypercholesterolemia
Hypocholesterolemia
Metabolic Syndrome
Other (altered fat metabolism)
Other (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
Cardiovascular Research
Internal/Organ Research
Metabolism Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Abcg5/Abcg8tm1Hobb
Allele Name		targeted mutation 1, Helen H Hobbs
Allele Type		Targeted (knock-out)
Common Name(s)		G5G8-;
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		SM1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Abcg5, ATP-binding cassette, sub-family G (WHITE), member 5
Chromosome		17
Gene Common Name(s)		AW112016; STSL; Sterolin-1; expressed sequence AW112016;
Molecular Note		Both the Abcg5 and Abcg8 endogenous loci, which are oriented head to head and separated by approximately 400 bp, were disrupted by the integration of a single targeting construct. A neomycin selection cassette flanked by both loxP and frt sites replaced s sequence extending from Abcg5 intron 2 into Abcg8 intron 3. The Walker A consensus sequences that make up a portion of the ATP binding sites in both genes were deleted. Northern and Western blot analyses indicated an absence of normal transcript and protein derived from both loci in homozygous mutant mice. [MGI Ref ID J:80679]
Gene Symbol and Name		Abcg8, ATP-binding cassette, sub-family G (WHITE), member 8
Chromosome		17
Gene Common Name(s)		1300003C16Rik; AI114946; GBD4; MGC142217; RIKEN cDNA 1300003C16 gene; STSL; Sterolin-2; expressed sequence AI114946;

Genotyping

Genotyping Information

Genotyping Protocols

Abcg5/Abcg8^tm1Hobb, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Yu L; Hammer RE; Li-Hawkins J; Von Bergmann K; Lutjohann D; Cohen JC; Hobbs HH. 2002. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci U S A 99(25):16237-42. [PubMed: 12444248]  [MGI Ref ID J:80679]

Additional References

Abcg5/Abcg8^tm1Hobb related

Calpe-Berdiel L; Rotllan N; Fievet C; Roig R; Blanco-Vaca F; Escola-Gil JC. 2008. Liver X receptor-mediated activation of reverse cholesterol transport from macrophages to feces in vivo requires ABCG5/G8. J Lipid Res 49(9):1904-11. [PubMed: 18509196]  [MGI Ref ID J:139767]

Wang J; Zhang DW; Lei Y; Xu F; Cohen JC; Hobbs HH; Xie XS. 2008. Purification and reconstitution of sterol transfer by native mouse ABCG5 and ABCG8. Biochemistry 47(18):5194-204. [PubMed: 18402465]  [MGI Ref ID J:134560]

Yang C; Yu L; Li W; Xu F; Cohen JC; Hobbs HH. 2004. Disruption of cholesterol homeostasis by plant sterols. J Clin Invest 114(6):813-22. [PubMed: 15372105]  [MGI Ref ID J:92860]

Yu L; Gupta S; Xu F; Liverman AD; Moschetta A; Mangelsdorf DJ; Repa JJ; Hobbs HH; Cohen JC. 2005. Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion. J Biol Chem 280(10):8742-7. [PubMed: 15611112]  [MGI Ref ID J:128570]

Yu L; von Bergmann K; Lutjohann D; Hobbs HH; Cohen JC. 2005. Ezetimibe normalizes metabolic defects in mice lacking ABCG5 and ABCG8. J Lipid Res 46(8):1739-44. [PubMed: 15930515]  [MGI Ref ID J:100478]

Yu L; von Bergmann K; Lutjohann D; Hobbs HH; Cohen JC. 2004. Selective sterol accumulation in ABCG5/ABCG8-deficient mice. J Lipid Res 45(2):301-7. [PubMed: 14657202]  [MGI Ref ID J:121052]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred mating heterozygote females to homozygote males. Homozygous breeder pair matings have been found to be unproductive by The Jackson Laboratory colony managers (February 3, 2005).

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery of Strains Needing Progeny Testing. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two untested males and two untested females (two pairs) will be recovered, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the overall recovery time to approximately 25 weeks. However, all pups recovered will be sent. Progeny testing is required to identify the genotype of mice of this strain, as a genotyping assay is not available. This type of testing involves breeding the recovered animals and assessing the phenotype of the offspring in order to identify animals carrying the mutation of interest. We can perform the progeny testing for you as a service or we can ship all recovered animals (at least two untested pairs) to you for progeny testing at your facility. If you perform the progeny testing, there is NO guarantee that a carrier will be identified. If we perform progeny testing as a service, additional breeding time will be required. In this case, when a male and female (one pair) are identified that carry the mutation, they and their offspring will be shipped. Delivery time for strains requiring progeny testing often exceeds 25 weeks and may take 12 months or more due to the difficulties in breeding some strains. The progeny testing cost is in addition to the recovery cost and is based on the number of boxes used and the time taken to produce the mice identified as carrying the mutation. Please note that identified pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Please contact Customer Service for more information on the cost of progeny testing for a strain: Tel: 1-800-422-6423 or 1-207-288-5845. Cryorecovery to establish a Dedicated Supply for greater quantities of mice One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
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.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.