Development of a Model of Chronic Kidney Disease in the C57BL/6 Mouse with Properties of Progressive Human CKD

Abstract

Chronic kidney disease (CKD) is a major healthcare problem with increasing prevalence in the population. CKD leads to end stage renal disease and increases the risk of cardiovascular disease. As such, it is important to study the mechanisms underlying CKD progression. To this end, an animal model was developed to allow the testing of new treatment strategies or molecular targets for CKD prevention. Many underlying risk factors result in CKD but the disease itself has common features, including renal interstitial fibrosis, tubular epithelial cell loss through apoptosis, glomerular damage, and renal inflammation. Further, CKD shows differences in prevalence between the genders with premenopausal women being relatively resistant to CKD. We sought to develop and characterize an animal model with these common features of human CKD in the C57BL/6 mouse. Mice of this genetic background have been used to produce transgenic strains that are commercially available. Thus, a CKD model in this strain would allow the testing of the effects of numerous genes on the severity or progression of CKD with minimal cost. This paper describes such a mouse model of CKD utilizing angiotensin II and deoxycorticosterone acetate as inducers.

Desoxycorticosterone pivalate‐salt treatment leads to non‐dipping hypertension in Per1 knockout mice

“…Thus the novel model presented in this study is the first single gene knockout model to produce a hypertensive non-dipping phenotype which develops quickly under normal light/dark conditions. In addition, WT C57Bl/6J mice are quite resistant to the current study regimen and usually require some additional insult to see a phenotype (Hartner et al, 2003, Mohammed-Ali et al, 2015), making the non-dipping exhibited by Per1 KO mice even more remarkable. Moreover, C57BL/6J Per1 KO mice are slightly hypertensive at baseline, which is a common characteristic of many non-dippers (Friedman and Logan, 2009), (Cakici et al, 2014).…”

Endoplasmic reticulum stress inhibition attenuates hypertensive chronic kidney disease through reduction in proteinuria

“…A combination of uninephrectomy, Ang II/DOCA infusion, as well as salt in the drinking water was used to induce CKD, as previously documented 8 54 . Briefly, 10-week-old male mice were subjected to a uninephrectomy under isofluorane anesthesia.…”

“…Blood pressure measurements were obtained through the tail cuff method using a CODA blood pressure analyzer (Kent Scientific), as done previously 54 . Metabolic cages were used to collect 24 h urine before the surgical procedure and after 3 weeks on treatment with AngII/DOCA/salt.…”

Euthanasia via CO2 inhalation causes premature cortical granule exocytosis in mouse oocytes and influences in vitro fertilization and embryo development

“…In this study, we first conducted a preliminary experiment on C57BL/6 donor female mice which are the most commonly used strain to create genetic modifications as human disease models (Huang, Scarpellini, Funck, Verderio, & Johnson, 2013;Mohammed-Ali et al, 2015). The C57BL/6 mice were euthanized by either L CO 2 or CD euthanasia, and the IVF and embryo development rates were determined.…”