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| These "Cyp 4a14" mutant mice may be useful studying kidney function and metabolism, cardiovascular physiology, hypertension, and the relationships between blood pressure, sex hormones, and p450 ω-hydroxylases. | |||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote (Female x Male) Species laboratory mouse Generation N11+F (28-APR-08) Donating Investigator Jorge Capdevila, Vanderbilt University Medical School Description
Mice homozygous for this "Cyp 4a14" mutant allele are viable and fertile. Homozygous deficiency of the targeted gene leads to spontaneous hypertension (more severe in males) that is androgen-sensitive. Homozygotes also exhibit other interrelated metabolic and regulatory effects; increased renal vascular resistance, impaired renal hemodynamics, elevated plasma androgens (5a-dihydrotestosterone (DHT) and testosterone), upregulated Cyp4a12 gene expression, and increased formation of prohypertensive 20-HETE. These "Cyp 4a14" mutant mice may be useful studying kidney function and metabolism, cardiovascular physiology, hypertension, and the relationships between blood pressure, sex hormones, and p450 ω-hydroxylases.Development
A targeting vector was designed to replace exons 10 and 11 of the targeted gene (coding for the heme-binding peptide) with a neomycin resistance cassette. The construct was electroporated into 129S6/SvEvTac-derived TL-1 embryonic stem (ES) cells. Correctly targeted ES cells were microinjected into blastocysts and the resulting chimeric mice were bred to 129S6/SvEvTac to generate heterozygotes. Mutants were then backcrossed to wildtype 129S6/SvEvTac mice for 11 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice may have been bred with 129S1/SvImJ (Stock No. 002448) to establish the colony.
Control Information
| Control | ||
|---|---|---|
| 002448 129S1/SvImJ | (approximate) | |
| Considerations for Choosing Controls | ||
Phenotype
Phenotype Information
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Cyp4a14tm1Jhc/Cyp4a14tm1Jhc
involves: 129S6/SvEvTac * 129X1/SvJ
- cardiovascular system phenotype
- abnormal renal vascular resistance (MGI Ref ID J:77631)
- reduced autoregulatory efficiency of kidney microvasculature
- increased renal vascular resistance (MGI Ref ID J:77631)
- decreased preglomerular arteriolar diameter in males
- abnormal vasoactive mediator physiology (MGI Ref ID J:77631)
- significantly higher rates of conversion of arachidonic acid to 20-hydroxyarachidonic acid in male kidneys due to up regulation of Cyp4a12
- little 20-hydroxyarachidonic acid activity on female kidneys
- castration reduces conversion of arachidonic acid to 20-hydroxyarachidonic acid in male kidneys
- decreased blood pressure (MGI Ref ID J:77631)
- castration reduces high blood pressure of males to normal levels
- increased blood pressure (MGI Ref ID J:77631)
- increased mean blood pressure in males
- increased blood pressure is spontaneous and insensitive to dietary salt
- female blood pressure shows less elevation and is more comparable to wild-type male blood pressure
- testosterone or dihydrotestosterone administration increases blood pressure of females and castrated males
- increased diastolic blood pressure (MGI Ref ID J:77631)
- in males
- increased systolic blood pressure (MGI Ref ID J:77631)
- in males
- renal/urinary system phenotype
- abnormal renal vascular resistance (MGI Ref ID J:77631)
- reduced autoregulatory efficiency of kidney microvasculature
- increased renal vascular resistance (MGI Ref ID J:77631)
- decreased preglomerular arteriolar diameter in males
This mouse can be used to support research in many areas including:
Cardiovascular Research
Hypertension
Metabolic Syndrome
Other
Vascular Defects
Endocrine Deficiency Research
Kidney Defects
Internal/Organ Research
Kidney Defects
Research Tools
Cardiovascular Research
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Cyp4a14tm1Jhc | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Jorge H Capdevila | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | 4a14(-); | ||
| Mutation Made By | Jorge Capdevila, Vanderbilt University Medical School | ||
| Strain of Origin | 129S6/SvEvTac | ||
| ES Cell Line Name | TL1/TL-1 | ||
| ES Cell Line Strain | 129S6/SvEvTac | ||
| Gene Symbol and Name | Cyp4a14, cytochrome P450, family 4, subfamily a, polypeptide 14 | ||
| Chromosome | 4 | ||
| Gene Common Name(s) | AI314743; CYPIVA3; expressed sequence AI314743; | ||
| Molecular Note | Exons 10 and 11, encoding the heme-binding domain, were deleted by the insertion of a neomycin selection cassette. The insertion introduced a frameshift mutation at codon 404 and generated a unique HindIII restriction site. [MGI Ref ID J:77631] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Cyp4a14tm1Jhc, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Holla VR; Adas F; Imig JD; Zhao X; Price E Jr; Olsen N; Kovacs WJ; Magnuson MA; Keeney DS; Breyer MD; Falck JR; Waterman MR; Capdevila JH. 2001. Alterations in the regulation of androgen-sensitive Cyp 4a monooxygenases cause hypertension. Proc Natl Acad Sci U S A 98(9):5211-6. [PubMed: 11320253] [MGI Ref ID J:77631]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice can be bred together. Mating System Homozygote x Homozygote (Female x Male) Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $155.70 Female or Male Homozygous for Cyp4a14tm1Jhc *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $311.40 Homozygous for Cyp4a14tm1Jhc x Homozygous for Cyp4a14tm1Jhc
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $202.50 Female or Male Homozygous for Cyp4a14tm1Jhc *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $404.90 Homozygous for Cyp4a14tm1Jhc x Homozygous for Cyp4a14tm1Jhc
Additional Supply Details
| Supply Notes |
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 002448 129S1/SvImJ | (approximate) | |
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
General Terms and Conditions
See Terms of Use
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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.Ordering and Purchasing Information
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Contact information
General inquiries
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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