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.
Shailendra B Patel, Medical College of Wisconsin
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Abcg5 | ATP binding cassette subfamily G member 5 |
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.
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.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression | Expression of lacZ has not been characterized (July, 2008) |
Allele Name | targeted mutation 1, Torsten Ploesch |
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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 |
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.
When using the B6.129P2-Abcg5tm1Plo/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008235 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wild-type for Abcg5<tm1Plo> |
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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