Cyp27a1tm1Elt mice (or sterol 27-hydroxylase-deficient mice) harbor a knock-out mutation of the cytochrome P450, family 27, subfamily a, polypeptide 1 locus that abolishes endogenous gene expression. These mice may be useful in studying the conversion of cholesterol to bile acids, as well as lipid and cholesterol homeostasis research.
Eran Leitersdorf, Hadassah University Hospital
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Cyp27a1 | cytochrome P450, family 27, subfamily a, polypeptide 1 |
These mice harbor a targeted mutation of the Cyp27a1 (cytochrome P450, family 27, subfamily a, polypeptide 1) locus that abolishes endogenous
gene expression. Homozygous mice (also called Cyp27a1-/-, cyp27-/-, or sterol 27-hydroxylase-deficient mice) are viable and fertile, with no RNA or protein expression from the targeted gene detected in liver tissue. Both formation of bile acids and excretion of fecal bile acids are decreased in homozygous mice. Compensatory up-regulation of hepatic enzymes that convert cholesterol to bile acids (bile acid synthesis) is also observed. Cyp27a1-/- mice exhibit a dramatic increase in cytochrome P450 3A (Cyp3a11) which catalyzes side-chain hydroxylations of bile acid intermediates subsequently facilitating their excretion in the bile and urine. Homozygous mice also have increased expression of other nuclear xenobiotic receptor PXR (pregnane X receptor) target genes.
A targeting vector was designed to replace a 71 bp fragment of the Cyp27a1 (cytochrome P450, family 27, subfamily a, polypeptide 1) locus in exon 8 (upstream to the putative heme-binding site that is crucial for the activity of P-450 enzymes) with a neomycin resistance gene cassette. This construct was electroporated into 129Sv-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6J mice to generate the mutant colony. The donating investigator reported that the cyp27-mutant colony was subsequently backcrossed to C57BL/6J inbred mice (see SNP note below) for approximately 12 generations prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
Allele Name | targeted mutation 1, Eran Leitersdorf |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Cyp27 -; cyp27-; Cyp27a1- |
Gene Symbol and Name | Cyp27a1, cytochrome P450, family 27, subfamily a, polypeptide 1 |
Gene Synonym(s) | |
Strain of Origin | 129/Sv |
Chromosome | 1 |
Molecular Note | A 71 bp fragment of exon 8 was deleted and replaced with a neomycin resistance gene via homologous recombination. The mutant allele was verified by Northern blot analysis of liver extracts from homozygous mutant mice. Western blot analysis of total liver mitochondrial protein from homozygous mutants confirmed the absence of protein product. |
Mutations Made By | Eran Leitersdorf, Hadassah University Hospital |
When maintaining a live colony, the donating investigator breeds heterozygous mice with wildtype siblings or C57BL/6J inbred mice (see Stock No. 000664). Homozygous mice may bred bred together.
When using the cyp27- mouse strain in a publication, please cite the originating article(s) and include JAX stock #009106 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Cyp27a1<tm1Elt> |
Frozen Mouse Embryo | B6.129-Cyp27a1<tm1Elt>/J | $2595.00 |
Frozen Mouse Embryo | B6.129-Cyp27a1<tm1Elt>/J | $2595.00 |
Frozen Mouse Embryo | B6.129-Cyp27a1<tm1Elt>/J | $3373.50 |
Frozen Mouse Embryo | B6.129-Cyp27a1<tm1Elt>/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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