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

Former Names B6;129-Cyp7b1tm1Rus/J    (Changed: 08-MAR-11 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?pN1 Generation Definitions   Donating Investigator Dr. David Russell,   Univ of Texas Southwest Med Ctr Dallas

Description
In this strain, a neomycin resistance (neo) cassette replaces part of exon 6 of the endogenous cytochrome P450, family 7, subfamily b, polypeptide 1 (Cyp7b1) gene, abolishing gene function. Homozygotes are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Cyp7b1 encodes oxysterol 7α-hydroxylase, an enzyme of the alternate bile acid synthesis pathway involved in cholesterol homeostasis. Plasma and tissue levels of 25- and 27-hydroxycholesterol, two oxysterol bioactive lipid substrates of oxysterol 7α-hydroxylase, were elevated in homozygotes. Sterol biosynthetic rates showed a 40% decrease in male kidneys. These mice are useful for studying cholesterol and bile acid metabolism, oxysterol synthesis and breakdown, macrophage function, and B cell trafficking and activation in the immune system.

Development
A targeting vector was designed to replace part of exon 6 encoding the cytochrome P450, family 7, subfamily b, polypeptide 1 (Cyp7b1) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129/SvEv-derived I1C embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. These mice were maintained on a mixed C57BL/6J x 129 background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Information

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

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Bile Acid Synthesis Defect, Congenital, 3; CBAS3   (CYP7B1) Spastic Paraplegia 5A, Autosomal Recessive; SPG5A   (CYP7B1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Cyp7b1^tm1Rus/Cyp7b1^tm1Rus

        involves: 129S/SvEv * C57BL/6J

• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype
  • both male and female homozygotes display normal bile acid metabolism   (MGI Ref ID J:62587)
  • also, both male and female homozygotes exhibit normal plasma cholesterol and triglyceride levels relative to wild-type   (MGI Ref ID J:62587)
  • the cholesterol contents of major tissues remain unaffected relative to wild-type   (MGI Ref ID J:62587)
• • abnormal cholesterol homeostasis
    • plasma and tissue levels of 25- and 27-hydroxycholesterol are significantly increased   (MGI Ref ID J:62587)
    • in vivo sterol biosynthetic rates remain relatively normal in most tissues with the exception of the male kidney, which shows a ~40% reduction in de novo synthesis relative to wild-type   (MGI Ref ID J:62587)
    • in contrast to levels of 25- and 27-hydroxycholesterol, which are significantly elevated, levels of another major oxysterol, 24-hydroxycholesterol, remain unaffected   (MGI Ref ID J:62589)
• immune system phenotype
• decreased IgA level
  • in the sera, lungs, and intestinal mucosa   (MGI Ref ID J:170807)

View Research Applications

Research Applications

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

Cardiovascular Research
Atherosclerosis
Metabolic Syndrome

Cell Biology Research
Protein Processing
Signal Transduction

Metabolism Research
Lipid Metabolism

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Cyp7b1tm1Rus
Allele Name		targeted mutation 1, David W Russell
Allele Type		Targeted (knock-out)
Common Name(s)		Cyp7b1-;
Mutation Made By		Dr. David Russell,   Univ of Texas Southwest Med Ctr Dallas
Strain of Origin		129S/SvEv
Gene Symbol and Name		Cyp7b1, cytochrome P450, family 7, subfamily b, polypeptide 1
Chromosome		3
Gene Common Name(s)		AW261589; CBAS3; CP7B; D3Ertd552e; DNA segment, Chr 3, ERATO Doi 552, expressed; SPG5A; expressed sequence AW261589; hct-1;
General Note		ES cell line = I1C.
Molecular Note		The gene was disrupted by replacing the majority of exon 6 (encoding amino acids 410-507) with a neomycin resistance cassette. Homozygous mutant animals lacked enzyme activity as determined by assay of hepatic lysates. Northern blot anlaysis of homozygous animals showed expression of mutant RNA species of larger size compared to wild-type, presumably from abnormal splicing of the gene product. Western blot analysis using polyclonal antibodies recognizing amino acids 266-281 did not detect protein productin liver homogenates from homozygous mutant animals. [MGI Ref ID J:62587]

Genotyping

Genotyping Information

Genotyping Protocols

Cyp7b1^tm1Rus, Melt Curve Analysis
Cyp7b1^tm1Rus, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Li-Hawkins J; Lund EG; Turley SD; Russell DW. 2000. Disruption of the oxysterol 7alpha-hydroxylase gene in mice. J Biol Chem 275(22):16536-42. [PubMed: 10748048]  [MGI Ref ID J:62587]

Additional References

Cyp7b1^tm1Rus related

Bauman DR; Bitmansour AD; McDonald JG; Thompson BM; Liang G; Russell DW. 2009. 25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production. Proc Natl Acad Sci U S A 106(39):16764-9. [PubMed: 19805370]  [MGI Ref ID J:170807]

Li-Hawkins J; Lund EG; Bronson AD; Russell DW. 2000. Expression cloning of an oxysterol 7alpha-hydroxylase selective for 24-hydroxycholesterol. J Biol Chem 275(22):16543-9. [PubMed: 10748047]  [MGI Ref ID J:62589]

Pettersson H; Lundqvist J; Oliw E; Norlin M. 2009. CYP7B1-mediated metabolism of 5alpha-androstane-3alpha,17beta-diol (3alpha-Adiol): a novel pathway for potential regulation of the cellular levels of androgens and neurosteroids. Biochim Biophys Acta 1791(12):1206-15. [PubMed: 19732851]  [MGI Ref ID J:164845]

Umetani M; Domoto H; Gormley AK; Yuhanna IS; Cummins CL; Javitt NB; Korach KS; Shaul PW; Mangelsdorf DJ. 2007. 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med 13(10):1185-92. [PubMed: 17873880]  [MGI Ref ID J:129931]

Yi T; Wang X; Kelly LM; An J; Xu Y; Sailer AW; Gustafsson JA; Russell DW; Cyster JG. 2012. Oxysterol Gradient Generation by Lymphoid Stromal Cells Guides Activated B Cell Movement during Humoral Responses. Immunity 37(3):535-48. [PubMed: 22999953]  [MGI Ref ID J:188276]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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