Expression of Cyp46a1 is disrupted in this tau-β-lacZ fusion protein knockin strain. These mice may be useful for studying cholesterol turnover in brain tissues.
Dr. David Russell, Univ of Texas Southwest Med Ctr Dallas
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Reporter, Null/Knockout) | Cyp46a1 | cytochrome P450, family 46, subfamily a, polypeptide 1 |
A tau-β-galactosidase (lacZ) fusion protein, followed by a neomycin (neo) resistance cassette, replaces the 3' end of exon 1 of the Cyp46a1 gene, abolishing gene function. Cyp46a1 encodes the enzyme cholesterol 24-hydroxylase which is expressed mainly in the brain, with low expression in liver. Cholesterol 24-hydroxylase is involved in cholesterol biosynthesis and turnover, and has also been implicated in the development of amyloid plaques in Alzheimer's disease. Homozygous mice are viable and fertile. In these mice, lacZ staining is evident in the spinal cord, midbrain, and hindbrain at E11.5, with expression decreasing between E11.5 and E13.5. LacZ staining is intensified between E11.5 and E13.5 in cells of the telencephalon, and the cerebral cortex. Beginning at E13.5, expression is restricted to dividing neurons in the neuroepithelium and post-mitotic neurons of the primordial plexiform layer of the telencephalon. These mice display a 40% reduction of new cholesterol synthesis in the brain, while maintaining cholesterol homeostasis in the central nervous system.
A targeting vector was designed to replace the 3' end of exon 1 of the cytochrome P450, family 46, subfamily a, polypeptide 1 (Cyp46a1) gene with a tau-β-galactosidase (lacZ) fusion protein and a neomycin (neo) resistance cassette. The construct was electroporated into 129S7/SvEvBrd-Hprt+-derived AB-1 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 background.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
---|---|
Site of Expression | lacZ is expressed throughout the brain. |
Allele Name | targeted mutation 1, David W Russell |
---|---|
Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | Cyp46a1- |
Gene Symbol and Name | Cyp46a1, cytochrome P450, family 46, subfamily a, polypeptide 1 |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Site of Expression | lacZ is expressed throughout the brain. |
Strain of Origin | 129S7/SvEvBrd-Hprt+ |
Chromosome | 12 |
Molecular Note | The 3 prime portion of exon 1 as well as a small part of intron 1 were replaced with DNA sequence encoding the N terminus of the bovine tau protein fused to the lacZ gene. mRNA for the targeted gene and its protein were undetectable in the brain of homozygous mice and were reduced in heterozygotes. |
Mutations Made By | Dr. David Russell, Univ of Texas Southwest Med Ctr Dallas |
When maintaining a live colony, homozygous mice may be bred together.
When using the B6;129S7-Cyp46a1tm1Rus/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017759 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Cyp46a1<tm1Rus> |
Frozen Mouse Embryo | B6;129S7-Cyp46a1<tm1Rus>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129S7-Cyp46a1<tm1Rus>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129S7-Cyp46a1<tm1Rus>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6;129S7-Cyp46a1<tm1Rus>/J Frozen Embryo | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.