These mice carry a knockout of the Rnls (renalase, FAD-dependent amine oxidase) gene. Homozygotes exhibit increased plasma catecholamine levels, hypertension, and mild ventricular hypertrophy in the absence of any measurable change in renal function.
Gary V Desir, Yale School of Medicine
The Rnls (renalase, FAD-dependent amine oxidase) gene encodes an oxidase that metabolizes catecholamines. It is expressed in kidney, heart, and skeletal muscle and secreted into the blood by the kidney. Levels of the protein are decreased in patients with chronic kidney disease (CKD) and end-stage renal disease.
These mice carry a knockout allele of the gene. Homozygotes demonstrate increased plasma catecholamine levels, hypertension, and mild ventricular hypertrophy in the absence of any measurable change in renal function. They tolerate cardiac ischemia poorly and develop myocardial necrosis threefold more severe than wildtype controls. This gene plays and important role in cardiovascular pathology.
Interestingly, in xenograft mouse models it has been shown that using a renalase monoclonal antibody shRNA knockdown of renalase inhibits pancreatic ductal adenocarcinoma growth.
Exons 1-4 were replaced by a neomycin resistance cassette, deleting the promoter and a large part of the coding region. The mutation was created in 129S1/Sv-Oca2+Tyr+Kitl+-derived W9.5 embryonic stem (ES) cells. Resultant chimeric males were bred to C57BL/6 females. This strain was maintained on a mixed C57BL/6 and 129S1 genetic background by the donating lab. Gene disruption was confirmed by genomic Southern blot, PCR, and western blot.
|Allele Name||targeted mutation 1, Gary V Desir|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Rnls, renalase, FAD-dependent amine oxidase|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||A neo cassette replaced exons 1 through 4. Western blot analysis confirmed the absence of protein expression in the kidney and heart.|
Heterozygotes and homozygotes are viable and fertile. Homozygotes have been reported to be active and mildly aggressive.
When using the B6;129S1-Rnlstm1Gvd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019578 in your Materials and Methods section.