Overview

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.

Donating Investigator

Shailendra B Patel, Medical College of Wisconsin

Genetic overview

Genetic Background	Generation

Abcg5^tm1Plo

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Abcg5	ATP binding cassette subfamily G member 5

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Research Applications

Research Tools
Reproductive Biology Research
Internal/Organ Research
Hematological Research
Cardiovascular Research
Metabolism Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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.

Expression Data

Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	Expression of lacZ has not been characterized (July, 2008)

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):290-300PubMed: 14699507 MGI: J:87209

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Genetics

Abcg5^tm1Plo

Allele Symbol: Abcg5^tm1Plo

Allele Name	targeted mutation 1, Torsten Ploesch
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	Abcg5^-
Gene Symbol and Name	Abcg5, ATP binding cassette subfamily G member 5
Gene Synonym(s)
Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	Expression of lacZ has not been characterized (July, 2008)
Strain of Origin	129P2/OlaHsd
Chromosome	17
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.
Mutations Made By	Shailendra Patel, Medical College of Wisconsin

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Diabetes and Obesity Research
  - lacZ
- lacZ Expression
- Cardiovascular Research
- Metabolism Research
- Internal/Organ Research
Reproductive Biology Research
- Fertility Defects
Internal/Organ Research
- Liver Defects
Hematological Research
- Platelet Defects
  - thrombocytopenia
Cardiovascular Research
- Vascular Defects
  - platelet defect
- Metabolic Syndrome
- Hypocholesterolemia
- Hypercholesterolemia
- Other
  - altered fat metabolism
  - altered lipoprotein profile
Metabolism Research
- Lipid Metabolism

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Abcg5^tm1Plo/Abcg5^tm1Plo
involves: 129P2/OlaHsd * C57BL/6J

growth/size/body region phenotype

enlarged liver
- liver is slightly increased in size compared to wild-type

liver/biliary system phenotype

abnormal liver physiology
- accumulation of plant sterols in the liver
- Normal - however, do not observe steatosis

enlarged liver
- liver is slightly increased in size compared to wild-type

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

abnormal phospholipid level
- phospholipid concentration in the gallbladder bile is decreased, however the cholesterol/phospholipid ratio is unchanged

decreased cholesterol level
- cholesterol content is reduced in gallbladder bile

decreased circulating cholesterol level
- 60% that of controls

increased circulating phytosterol level
- 37- and 7.7-fold increase of the plant sterols beta-sitosterol and campesterol , respectively, in the plasma relative to controls
- plasma levels of the plant sterols stigmasterol and brassicasterol are increased
- plasma plant sterol concentrations are further elevated when treated with the synthetic LXR agonist T0901317 unlike in wild-type where they are lowered

increased circulating triglyceride level
- plasma triglycerides are elevated, predominantly in the very-low-density lipoprotein-sized lipoprotein fractions

increased circulating VLDL triglyceride level

Genotype: Abcg5^tm1Plo/Abcg5^tm1Plo
involves: 129P2/OlaHsd

growth/size/body region phenotype

increased liver weight
- liver weights are slightly increased, however this is not due to steatosis as triglyceride levels are not increased

homeostasis/metabolism phenotype

abnormal cholesterol homeostasis
- expression of cholesterol metabolism genes in the liver is altered

abnormal lipid homeostasis
- basal biliary phospholipid secretion rates are decreased by 35%
- basal biliary sterol secretion rates are decreased by 82%

liver/biliary system phenotype

abnormal bile secretion
- basal biliary phospholipid secretion rates are decreased by 35%
- basal biliary sterol secretion rates are decreased by 82%
- exhibit increased bile flow after the creation of a gallbladder fistula, however bile salt output rates and biliary bile salt composition are unaffected

abnormal liver physiology
- 45% reduction in liver sterol ester concentrations
- do not exhibit an increase in sterol secretion when fed the LXR agonist T0901317, as is seen with wild-type

increased liver weight
- liver weights are slightly increased, however this is not due to steatosis as triglyceride levels are not increased

References

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):290-300PubMed: 14699507 MGI: J:87209

Additional - Abcg5^tm1Plo related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Abcg5
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129P2-Abcg5^tm1Plo/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008235 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Abcg5<tm1Plo>

Related Products and Services

Frozen Mouse Embryo	B6.129P2-Abcg5<tm1Plo>/J	$2595.00
Frozen Mouse Embryo	B6.129P2-Abcg5<tm1Plo>/J	$2595.00
Frozen Mouse Embryo	B6.129P2-Abcg5<tm1Plo>/J	$3373.50
Frozen Mouse Embryo	B6.129P2-Abcg5<tm1Plo>/J	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Abcg5tm1Plo

Allele Symbol: Abcg5tm1Plo

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Abcg5tm1Plo/Abcg5tm1Ploinvolves: 129P2/OlaHsd * C57BL/6J

growth/size/body region phenotype

liver/biliary system phenotype

homeostasis/metabolism phenotype

Genotype: Abcg5tm1Plo/Abcg5tm1Ploinvolves: 129P2/OlaHsd

growth/size/body region phenotype

homeostasis/metabolism phenotype

liver/biliary system phenotype

References

Additional - Abcg5tm1Plo related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Abcg5^tm1Plo

Allele Symbol: Abcg5^tm1Plo

Genotype: Abcg5^tm1Plo/Abcg5^tm1Plo
involves: 129P2/OlaHsd * C57BL/6J

Genotype: Abcg5^tm1Plo/Abcg5^tm1Plo
involves: 129P2/OlaHsd

Additional - Abcg5^tm1Plo related