Description

Strain Information

Former Names B6SJL-Tg(ABCG5/ABCG8)14-2Hobb    (Changed: 15-DEC-04 ) Type Mutant Stock; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Hemizygote         (Female x Male) Species laboratory mouse   Donating Investigator Helen Hobbs,   UT Southwestern Medical Center

Description
These transgenic mice over-express the human ABCG5 and ABCG8 genes under the direction of their endogenous regulatory sequences. Copy number of the transgene was estimated using Southern blot analysis to compare transgenic mouse genomic DNA to human genomic DNA. These transgenic mice have approximately ten copies of the transgene. Northern blot analysis revealed the human transgene is expressed in the liver and small intestine. RT-PCR showed trace levels of transgene transcript in ovary tissue. Absorption of dietary cholesterol in transgenic mice is reduced by 50%. Mean fasting plasma cholesterol levels are significantly lower in female transgenic mice. Excretion of neutral sterols in feces is elevated to three times higher above normal in male transgenic mice and six times higher in female transgenic mice. Bile from transgenic animals is opaque as compared to the clear bile of wildtype animals. Cholesterol in the bile is elevated to levels five times higher than normal in male transgenic mice and seven times higher in female transgenic mice. The phospholipid level in the bile of male transgenic mice is slightly increased. When fed a high-cholesterol diet, transgenic mice did not exhibit any significant change in hepatic cholesterol levels. Genes encoding proteins involved in cholesterol synthesis are up regulated. Mice homozygous for the transgenic insert are viable and fertile. This mutant mouse strain may be useful in studies of cholesterol trafficking and cholesterol gallstone disease.

Development
A transgenic construct containing a 90kb of sequence including the entire coding regions of the human ABCG5 and ABCG8 genes, approximately 30Kb of sequence flanking the 3' end of ABCG5, 6Kb of sequence flanking the 3" end of ABCG8 and sequence encoding exons 6 to 13 of putative gene CGI-60 was injected into fertilized C57BL/6J X SJL F2 (Stock # 100012) mouse eggs. Founder animals were bred to C57BL/6J X SJL F1 mice.

Control Information

	Control
	Noncarrier
Considerations for Choosing Controls

Phenotype

Phenotype Information

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)

Cell Biology Research
Channel and Transporter Defects

Internal/Organ Research
Liver Defects
Other

Research Tools
Cardiovascular Research
Internal/Organ Research
Metabolism Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(ABCG5/ABCG8)14-2Hobb
Allele Name		transgene insertion 14-2, Helen H Hobbs
Allele Type		Transgenic (random, expressed)
Common Name(s)		ABCG5/ABCG8; G5G8Tg; hG5G8Tg;
Mutation Made By		Liqing Yu,   Wake Forest Univ. School of Medicine
Strain of Origin		(C57BL/6J x SJL)F2
Expressed Gene		ABCG8, ATP-binding cassette, sub-family G (WHITE), member 8, human
Expressed Gene		ABCG5, ATP-binding cassette, sub-family G (WHITE), member 5, human
General Note		Transgenic mice over express the human ABCG5 and ABCG8 genes under the direction of their endogenous regulatory sequences. These mice have approximately ten copies of the transgene. Absorption of dietary cholesterol in transgenic mice is reduced by 50%.Mean fasting plasma cholesterol levels are significantly lower in female transgenic mice. Excretion of neutral sterols in feces is elevated to three times higher above normal in male transgenic mice and six times higher in female transgenic mice. Bile from transgenic animals is opaque as compared to the clear bile of wildtype animals. Cholesterol in the bile is elevated to levels five times higher than normal in male transgenic mice and seven times higher in female transgenic mice. The phospholipid levelin the bile of male transgenic mice is slightly increased. When fed a high-cholesterol diet, transgenic mice did not exhibit any significant change in hepatic cholesterol levels. Genes encoding proteins involved in cholesterol synthesis are up regulated.Mice homozygous for the transgenic insert are viable and fertile.
Molecular Note		The transgene contains a 90kb of sequence including the entire coding regions of the human ABCG5 and ABCG8 genes, approximately 30Kb of sequence flanking the 3' end of ABCG5, 6Kb of sequence flanking the 3' end of ABCG8 and sequence encoding exons 6 to 13 of a putative gene called CGI-60. Estimated transgene copy number is ~14 for this line. Northern blot analysis revealed the human transgene is expressed in the liver and small intestine. RT-PCR showed trace levels of transgene transcript in ovary tissue. [MGI Ref ID J:78963]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(ABCG5/ABCG8)14-2Hobb, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Yu L; Li-Hawkins J; Hammer RE; Berge KE; Horton JD; Cohen JC; Hobbs HH. 2002. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest 110(5):671-80. [PubMed: 12208868]  [MGI Ref ID J:78963]

Additional References

Tg(ABCG5/ABCG8)14-2Hobb related

Langheim S; Yu L; von Bergmann K; Lutjohann D; Xu F; Hobbs HH; Cohen JC. 2005. ABCG5 and ABCG8 require MDR2 for secretion of cholesterol into bile. J Lipid Res 46(8):1732-8. [PubMed: 15930516]  [MGI Ref ID J:100491]

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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	A transgenic construct containing the entire coding regions of the human ABCG5 and ABCG8 genes was used to create transgenic animals on a B6SJL background. The strain is maintained as a hemizygote.
Mating System	+/+ sibling x Hemizygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

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

Cryorecovery - Standard. 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 males and two females (two pairs) will be provided, 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 delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that 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. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. 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
	Noncarrier
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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Terms of Use

Terms of Use

General Terms and Conditions

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Contact information

General inquiries

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

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“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.”

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