129S-Cyp4a14^tm1Jhc/J

Stock number: 007175
Research areas: Cardiovascular Research, Endocrine Deficiency Research, Internal/Organ Research, Research Tools

Description

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.

Detailed 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 (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.

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.

Allele

Symbol: Cyp4a14^tm1Jhc
Name: targeted mutation 1, Jorge H Capdevila
MGI accession ID: MGI:2183240
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cyp4a14
Marker name: cytochrome P450, family 4, subfamily a, polypeptide 14
Chromosome: 4
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.