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5/6 nephrectomy induces different renal, cardiac and vascular consequences in 129/Sv and C57BL/6JRj mice.

ABSTRACT: Experimental models of cardiovascular diseases largely depend on the genetic background. Subtotal 5/6 nephrectomy (5/6 Nx) is the most frequently used model of chronic kidney disease (CKD) in rodents. However, in mice, cardiovascular consequences of 5/6 Nx are rarely reported in details and comparative results between strains are scarce. The present study detailed and compared the outcomes of 5/6 Nx in the 2 main strains of mice used in cardiovascular and kidney research, 129/Sv and C57BL/6JRj. Twelve weeks after 5/6 Nx, CKD was demonstrated by a significant increase in plasma creatinine in both 129/Sv and C57BL/6JRj male mice. Polyuria and kidney histological lesions were more pronounced in 129/Sv than in C57BL/6JRj mice. Increase in albuminuria was significant in 129/Sv but not in C57BL/6JRj mice. Both strains exhibited an increase in systolic blood pressure after 8 weeks associated with decreases in cardiac systolic and diastolic function. Heart weight increased significantly only in 129/Sv mice. Endothelium-dependent mesenteric artery relaxation to acetylcholine was altered after 5/6 Nx in C57BL/6JRj mice. Marked reduction of endothelium-dependent vasodilation to increased intraluminal flow was demonstrated in both strains after 5/6 Nx. Cardiovascular and kidney consequences of 5/6 Nx were more pronounced in 129/Sv than in C57BL/6JRj mice.

SUBMITTER: Hamzaoui M

PROVIDER: S-EPMC6992698 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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5/6 nephrectomy induces different renal, cardiac and vascular consequences in 129/Sv and C57BL/6JRj mice.

Hamzaoui Mouad M Djerada Zoubir Z Brunel Valery V Mulder Paul P Richard Vincent V Bellien Jérémy J Guerrot Dominique D

Scientific reports 20200130 1

Experimental models of cardiovascular diseases largely depend on the genetic background. Subtotal 5/6 nephrectomy (5/6 Nx) is the most frequently used model of chronic kidney disease (CKD) in rodents. However, in mice, cardiovascular consequences of 5/6 Nx are rarely reported in details and comparative results between strains are scarce. The present study detailed and compared the outcomes of 5/6 Nx in the 2 main strains of mice used in cardiovascular and kidney research, 129/Sv and C57BL/6JRj. ...[more]

PMID: 32001792

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Project description:BackgroundIn the recent years, the use of Doppler-echocardiography has become a standard non-invasive technique in the analysis of cardiac malformations in genetically modified mice. Therefore, normal values have to be established for the most commonly used inbred strains in whose genetic background those mutations are generated. Here we provide reference values for transthoracic echocardiography measurements in juvenile (3 weeks) and adult (8 weeks) 129/Sv mice.MethodsEchocardiographic measurements were performed using B-mode, M-mode and Doppler-mode in 15 juvenile (3 weeks) and 15 adult (8 weeks) mice, during isoflurane anesthesia. M-mode measurements variability of left ventricle (LV) was determined.ResultsSeveral echocardiographic measurements significantly differ between juvenile and adult mice. Most of these measurements are related with cardiac dimensions. All B-mode measurements were different between juveniles and adults (higher in the adults), except for fractional area change (FAC). Ejection fraction (EF) and fractional shortening (FS), calculated from M-mode parameters, do not differ between juvenile and adult mice. Stroke volume (SV) and cardiac output (CO) were significantly different between juvenile and adult mice. SV was 31.93 ± 8.67 ?l in juveniles vs 70.61 ± 24.66 ?l in adults, ? < 0.001. CO was 12.06 ± 4.05 ml/min in juveniles vs 29.71 ± 10.13 ml/min in adults, ? < 0.001. No difference was found in mitral valve (MV) and tricuspid valve (TV) related parameters between juvenile and adult mice. It was demonstrated that variability of M-mode measurements of LV is minimal.ConclusionsThis study suggests that differences in cardiac dimensions, as wells as in pulmonary and aorta outflow parameters, were found between juvenile and adult mice. However, mitral and tricuspid inflow parameters seem to be similar between 3 weeks and 8 weeks mice. The reference values established in this study would contribute as a basis to future studies in post-natal cardiovascular development and diagnosing cardiovascular disorders in genetically modified mouse mutant lines.

Project description:In laboratory animal facilities, it is a common code of practice to house female mice in groups. However, some experimental conditions require to house them individually, even though social isolation may impair their well-being. Therefore, we introduced a separated pair housing system and investigated whether it can refine single housing of adult female C57BL/6JRj mice. Individually ventilated cages (IVC) were divided by perforated transparent walls to separate two mice within a cage. The cage divider allowed visual, acoustic, and olfactory contact between the mice but prevented interindividual body-contact or food sharing. Short- and long-term effects of the separated pair housing system on the well-being of the mice were compared with single and group housing using a range of behavioral and physiological parameters: Nest building behavior was assessed based on the complexity of nests, the burrowing performance was measured by the amount of food pellets removed from a bottle, and trait anxiety-related behavior was tested in the free exploratory paradigm. For the evaluation of the ease of handling, interaction with the experimenter's hand was monitored. Social interaction with unknown conspecifics and locomotor activity were investigated in a test arena. Moreover, body weight and stress hormone (metabolites) were measured in feces and hair. After the mice spent a day under the respective housing conditions, concentrations of fecal corticosterone metabolites were higher in separated pair-housed mice, and they built nests of a higher complexity when compared to single-housed mice. The latter effect was still observable eight weeks later. In week 8, separated pair-housed mice showed less locomotor activity in the social interaction arena compared to mice from the other housing systems, i.e., single and group housing. Regardless of the time of testing, pair housing improved the burrowing performance. Separated pair-housed mice were more difficult to catch than group-housed mice. Hair corticosterone, progesterone, and dehydroepiandrosterone concentrations changed with increasing age independently of the housing system. There were no effects of the housing systems on trait anxiety-related behavior in the free exploratory paradigm, voluntary interaction with the experimenter's hand, and body weight. Overall, the transfer to the separated pair housing system caused short-term stress responses in female C57BL/6JRj mice. Long-term effects of separated pair housing were ambiguous. On one hand, separated pair housing increased nesting and burrowing behavior and may therefore be beneficial compared to single housing. But on the other hand, locomotor activity decreased. The study underlined that the effects of the housing conditions on physiological and behavioral parameters should be considered when analyzing and reporting animal experiments.

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5/6 nephrectomy induces different renal, cardiac and vascular consequences in 129/Sv and C57BL/6JRj mice.

Publications

5/6 nephrectomy induces different renal, cardiac and vascular consequences in 129/Sv and C57BL/6JRj mice.

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