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.
Jorge H. Capdevila, Vanderbilt University Medical School
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 (5α-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.
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.
|Allele Name||targeted mutation 1, Jorge H Capdevila|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Cyp4a14, cytochrome P450, family 4, subfamily a, polypeptide 14|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Exons 10 and 11, encoding the heme-binding domain, were replaced with a neomycin selection cassette. The insertion introduced a frameshift mutation at codon 404 and generated a unique HindIII restriction site.|
|Mutations Made By|| |
Jorge Capdevila, Vanderbilt University Medical School
When maintaining a live colony, homozygous mice can be bred together.
When using the 129S-Cyp4a14tm1Jhc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007175 in your Materials and Methods section.