Mouse Chromosome 7 Harbors a Quantitative Trait Locus for Isoflurane Minimum Alveolar Concentration

Cascio, Michael J.; Xing, Yanpeng; Gong, Diane; Popovich, John; Eger, Edmond I.; Sen, Sáunak; Peltz, Gary; Sonner, James M.

doi:10.1213/01.ane.0000261277.65343.4e

Cited by 10 publications

(7 citation statements)

References 19 publications

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“…The rectal temperature was periodically checked to ensure maintenance of normothermia (Fisher Scientific, Pittsburgh, PA) at 37±0.5°C. The level of exposure for sevoflurane was determined after calculating the minimum alveolar concentration (MAC) equivalent to isoflurane 18-20. The 0.75% isoflurane or 1.1% sevoflurane is about equipotent to ~0.5 MAC in mice.…”

Section: Methodsmentioning

confidence: 99%

Isoflurane Causes Greater Neurodegeneration Than an Equivalent Exposure of Sevoflurane in the Developing Brain of Neonatal Mice

Ge¹,

et al. 2010

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Background We hypothesized that isoflurane has a greater potency to induce neurodegeneration than sevoflurane in the developing brains of neonatal mice based on our previous studies in cell culture. Methods We treated 7-day-old mice with either 0.75% isoflurane or 1.1% sevoflurane (~0.5 Minimum Alveolar Concentration) for 6 h and then obtained blood and brain samples at 2 h after the anesthesia treatment for determination of neuroapoptosis in different brain regions and the neurodegenerative biomarker S100β in the blood. The mechanisms of neurodegeneration induced by isoflurane or sevoflurane were also compared by determining protein expressions of the cell cycle, and apoptosis related proteins. In separate groups, memory and learning ability were evaluated through the use of Morris Water Maze testing in mice at postnatal day 42 after anesthesia treatment at postnatal day 7. Results Isoflurane but not sevoflurane significantly increased the neurodegenerative biomarker S100β in the blood. Isoflurane treatments significantly increased apoptosis indicated by the activation of caspase-3 and elevation of Poly-(ADP-ribose) polymerase in different brain regions. An equipotent exposure of sevoflurane tended to increase apoptosis in hippocampal and cortex areas but was significantly less potent than isoflurane. Neither isoflurane nor sevoflurane changed protein levels of glyceraldehyde-3-phosphate dehydrogenase, beta-site amyloid beta precursor protein cleaving enzyme and cell cycle regulatory proteins (CDK4, cyclin D1) significantly. Isoflurane and sevoflurane at the selected exposures did not significantly alter memory and learning ability. Conclusion At equipotent exposures, isoflurane has a greater potency than sevoflurane to cause neurodegeneration in the developing brains of neonatal mice.

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Section: Methodsmentioning

confidence: 99%

Isoflurane Causes Greater Neurodegeneration Than an Equivalent Exposure of Sevoflurane in the Developing Brain of Neonatal Mice

Ge¹,

et al. 2010

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“…Individual mongrel cats show differential sensitivity to modern VGAs 8 as do segregated human populations for SEVO 9 – 11 . These data raise the possibility that anesthetic sensitivity may behave like a quantitative trait 12 , 13 , as opposed to being mediated by a small number of discrete molecular targets. By contrast, Mendelian mutations have pronounced effects on the sensitivity to VGAs in model organisms 14 – 16 and can result in life-threatening consequences 17 , 18 .…”

Section: Introductionmentioning

confidence: 98%

Genetic variability affects absolute and relative potencies and kinetics of the anesthetics isoflurane and sevoflurane in Drosophila melanogaster

Olufs

Loewen

Ganetzky

et al. 2018

Sci Rep

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Genetic variability affects the response to numerous xenobiotics but its role in the clinically-observed irregular responses to general anesthetics remains uncertain. To investigate the pharmacogenetics of volatile general anesthetics (VGAs), we developed a Serial Anesthesia Array apparatus to expose multiple Drosophila melanogaster samples to VGAs and behavioral assays to determine pharmacokinetic and pharmacodynamic properties of VGAs. We studied the VGAs isoflurane and sevoflurane in four wild type strains from the Drosophila Genetic Reference Panel, two commonly used laboratory strains (Canton S and w1118), and a mutant in Complex I of the mitochondrial electron transport chain (ND2360114). In all seven strains, isoflurane was more potent than sevoflurane, as predicted by their relative lipid solubilities, and emergence from isoflurane was slower than from sevoflurane, reproducing cardinal pharmacokinetic and pharmacodynamic properties in mammals. In addition, ND2360114 flies were more sensitive to both agents, as observed in worms, mice, and humans carrying Complex I mutations. Moreover, we found substantial variability among the fly strains both in absolute and in relative pharmacokinetic and pharmacodynamic profiles of isoflurane and sevoflurane. These data indicate that naturally occurring genetic variations measurably influence cardinal pharmacologic properties of VGAs and that flies can be used to identify relevant genetic variations.

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“…Champy et al [ 57 ] reported that circulating total cholesterol levels were significantly higher in unanesthetized male C57BL/6J mice when compared to isoflurane anesthetized counterparts. Since inbred strains of mice differ in their sensitivity for isoflurane and a QTL for this phenotype has been described [ 87 ], it can be argued that the use of anesthesia influence the chromosomal assignment of QTLs for baseline circulating total cholesterol level in mice.…”

Section: Resultsmentioning

confidence: 99%

Chromosomal assignment of quantitative trait loci influencing baseline circulating total cholesterol level in male laboratory mice: report of a consomic strain survey and comparison with published results

et al. 2015

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BackgroundAn important risk for atherosclerosis is a low level of HDL cholesterol. Baseline HDL cholesterol is under complex genetic and environmental control. Here we report on results of male mice from a consomic strain survey and the parental inbred strains for baseline circulating total cholesterol concentration, which is almost the same as HDL cholesterol in chow fed mice. The consomic strains have been derived from C57BL/6J (host strain) and A/J (donor strain) inbred lines. The work contributes to the value of the mouse as an animal model for studying the genetic background of differences in baseline circulating total and HDL cholesterol levels.ResultsThe consomic strain survey suggested that mouse chromosomes 1, 7, 9, 14, 16, 17, 19, X, and Y contained at least one quantitative trait locus that is involved in baseline circulating total cholesterol concentration. All consomic lines, for which there is evidence that the substituted chromosome contains a quantitative trait locus, increase compared to the host strain baseline circulating total cholesterol concentration. Since there is evidence that ‘body weight’, ‘age at blood sampling’, ‘time of the day blood was collected’, and ‘season’ influence this phenotype, additional statistical analyses (with these variables as covariates) were performed. Now there is only evidence for quantitative trait loci on chromosomes 1, 8, 12, and Y. Taken the present results together with previous consomic strain surveys there is evidence that all mouse chromosomes carry quantitative trait loci that control baseline circulating total cholesterol levels. There was however little agreement between the present consomic strain results and previous sets of data. This might be explained by seasonal effects and differences in methodological variables such as age of the mice, fasting versus non-fasting, percentage of dietary fat, unanesthetized versus anesthetized mice, and the daily light–dark cycle.ConclusionsThe present findings, when compared with previous consomic strain surveys, clearly illustrate the complexity of the genetic-environmental architecture for the regulation of baseline circulating total cholesterol levels in mice. Different data can be obtained from different labs and it underscores that animal geneticists should present as accurate a picture as possible of the laboratory mouse’s environment.

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Mouse Chromosome 7 Harbors a Quantitative Trait Locus for Isoflurane Minimum Alveolar Concentration

Abstract: Both methods of genetic analysis identified a QTL for isoflurane MAC that was located on the proximal part of mouse chromosome 7.

Cited by 10 publications

References 19 publications

Isoflurane Causes Greater Neurodegeneration Than an Equivalent Exposure of Sevoflurane in the Developing Brain of Neonatal Mice

Isoflurane Causes Greater Neurodegeneration Than an Equivalent Exposure of Sevoflurane in the Developing Brain of Neonatal Mice

Genetic variability affects absolute and relative potencies and kinetics of the anesthetics isoflurane and sevoflurane in Drosophila melanogaster

Chromosomal assignment of quantitative trait loci influencing baseline circulating total cholesterol level in male laboratory mice: report of a consomic strain survey and comparison with published results

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