What is the clinical evidence from this study?

Study design: Other. Population: Cardiac function in inbred mouse strains. Intervention: Inbred mouse strain genetic background vs. C57BL/6J. Primary outcome: Cardiac function (ex vivo isolated Langendorff heart preparation and in vivo real-time hemodynamic analysis).

July 14, 2010Open Access

Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains

Key Result

Significant strain-dependent differences in cardiac function were observed, with C57BL/6J mice maintaining better function after ex vivo ischemia but showing dramatic decompensation during in vivo acute hypoxia compared to other strains.

Structured PICO

Does genetic background influence ex vivo and in vivo cardiac function in commonly used inbred mouse strains?

Population

Male mice aged 4-6 months from eight commonly used inbred strains were evaluated for baseline cardiac function and response to physiological stress.

Exposure

Ex vivo isolated Langendorff heart preparation with global ischemia/reperfusion, and in vivo real-time hemodynamic analysis using conductance micromanometry with esmolol infusion and acute hypoxic challenge.

Comparator

C57BL/6J strain used as the reference comparator for the other 7 inbred strains.

Outcome

Ex vivo and in vivo cardiac function (including LVDP, LVSP, dP/dt, EF, LVEDP) at baseline and in response to ischemia/reperfusion, esmolol infusion, and acute hypoxia.surrogate

Genetic background significantly influences baseline cardiac function and the response to physiological stress in mice, which is critical for interpreting cardiovascular phenotypes in genetically modified models.

Limitations

Differences between ex vivo and in vivo preparations, including lack of physiological loading and autonomic innervation ex vivo
Use of different anesthetics (pentobarbital vs isoflurane) which may have strain-dependent cardiodepressive or cardioprotective effects

Abstract

Inbred mouse strains play a critical role in biomedical research. Genetic homogeneity within inbred strains and their general amenability to genetic manipulation have made them an ideal resource for dissecting the physiological function(s) of individual genes. However, the inbreeding that makes inbred mice so useful also results in genetic divergence between them. This genetic divergence is often unaccounted for but may be a confounding factor when comparing studies that have utilized distinct inbred strains. Here, we compared the cardiac function of C57BL/6J mice to seven other commonly used inbred mouse strains: FVB/NJ, DBA/2J, C3H/HeJ, BALB/cJ, 129X1/SvJ, C57BL/10SnJ, and 129S1/SvImJ. The assays used to compare cardiac function were the ex vivo isolated Langendorff heart preparation and in vivo real-time hemodynamic analysis using conductance micromanometry. We report significant strain-dependent differences in cardiac function between C57BL/6J and other commonly used inbred strains. C57BL/6J maintained better cardiac function than most inbred strains after ex vivo ischemia, particularly compared with 129S1/SvImJ, 129X1/SvJ, and C57BL/10SnJ strains. However, during in vivo acute hypoxia 129X1/SvJ and 129S1/SvImJ maintained relatively normal cardiac function, whereas C57BL/6J animals showed dramatic cardiac decompensation. Additionally, C3H/HeJ showed rapid and marked cardiac decompensation in response to esmolol infusion compared with effects of other strains. These findings demonstrate the complex effects of genetic divergence between inbred strains on cardiac function. These results may help inform analysis of gene ablation or transgenic studies and further demonstrate specific quantitative traits that could be useful in discovery of genetic modifiers relevant to cardiac health and disease.

Demander à l'IA

Bookmark

View Full Paper