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GENERAL ARTICLES

Mouse Strain Modestly Influences Minimum Alveolar Anesthetic Concentration and Convulsivity of Inhaled Compounds

Department of Anesthesia, University of California, San Francisco, California

Address correspondence to Dr. James M. Sonner, Department of Anesthesia, 513 Parnassus Ave., Box 0464, University of California, San Francisco, CA 94143-0464. Address e-mail to jim_sonner{at}quickmail.ucsf.edu

	Abstract

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In this study, we measured the minimum alveolar anesthetic concentration (MAC) in several mouse strains, including strains used in the construction of genetically engineered mice. This is important because defined genetic modifications are used increasingly to test mechanisms of inhaled anesthetic action, and background variability in MAC can potentially influence the interpretation of these studies. We investigated the effect of strain on MAC for desflurane, isoflurane, halothane, ethanol, the experimental anesthetic 1-chloro-1,2,2-trifluorocyclobutane, and convulsive 50% effective dose (the dose required to produce convulsions in 50% of animals) of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane. These drugs were studied in eight inbred strains, including both laboratory and wild mouse strains (129/J, 129/SvJ, 129/Ola Hsd, C57BL/6NHsd, C57BL/6J, DBA/2J, Spret/Ei, and Cast/Ei), one hybrid strain (B6129F2/J, derived from the C57BL/6J and 129/J strains), and one outbred strain (CD-1). To test our ability to detect effects in a genetically modified mouse, we compared these data with those for a mouse lacking the (neuronal) isoform of the protein kinase C gene (PKC). We also assessed whether amputating the tail tip of mice (a standard method of obtaining tissue for genetic analysis) increased MAC (e.g., by sensitization of the spinal cord). MAC and convulsant 50% effective dose values differed modestly among strains, with a range of 17% to 39% from the lowest to highest values for MAC using conventional anesthetics, and up to 48% using the experimental anesthetic 1-chloro-1,2,2-trifluorocyclobutane. Convulsivity to the nonimmobilizer varied by 47%. Amputating the tail tip did not affect MAC. PKC knockout mice had significantly higher MAC values than control animals for isoflurane, but not for halothane or desflurane, which implies that protein phosphorylation by PKC can alter sensitivity to isoflurane.

Implications: Anesthetic potency differs by modest amounts among inbred, outbred, wild, and laboratory mouse strains. Absence of the neural form of protein kinase C increases minimum alveolar anesthetic concentration for isoflurane, indicating that protein phosphorylation by the -isoform of protein kinase C (PKC) can influence the potency of this anesthetic.

	Introduction

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Mouse strains differ from each other in behavior, neurobiology, and pharmacology. The genetic polymorphisms underlying these variations in phenotype are of interest because of the increasing use of genetically modified mice to probe the molecular basis of drug effects, disease, and behavior. Of immediate relevance, tests of molecular mechanisms of inhaled anesthetic action now apply gene targeting technology (1). Differences for anesthetic endpoints among mouse strains are germane to this endeavor because mice bearing induced mutations typically are derived from more than one inbred strain. The mixed genetic background in the resulting mutant mice can influence the phenotype expressed by otherwise well defined mutations.

The minimum alveolar anesthetic concentration (MAC) of inhaled anesthetic required to eliminate movement in 50% of subjects in response to a noxious stimulus is a standard, commonly measured endpoint of inhaled anesthetic requirement. Various factors influence MAC (2), including species and within-species, strain. For rats, MAC among different strains may differ by 25% to 30% (3). Mice bred for greater and lesser sensitivity to the effect of nitrous oxide on the righting reflex may differ by approximately 50% (4).

The present study measured MAC in eight inbred laboratory mouse strains, including those used to create genetically modified mice. For comparison, we also studied wild mice, one hybrid strain derived from two of the inbred laboratory strains and one outbred strain. As a preliminary assessment of our ability to identify differences in anesthetic potency in genetically engineered mice, we determined MAC in mice knocked out for the -isoform of protein kinase C (PKC). We chose these animals because they have decreased sensitivity to ethanol, as assessed by loss of righting reflex and development of hypothermia (5). We hypothesized that these mice would be less sensitive to the immobilizing effects of anesthetics and therefore have higher MAC values than the other test strains. Finally, because genetically modified animals have the tips of their tails amputated to provide tissue for genetic analysis, and such trauma might lead to sensitization of the spinal cord (and therefore alter our measurements of anesthetic potency), we also measured anesthetic MAC in control animals before and after clipping the tips of their tails.

Responses of the inbred, outbred, and hybrid mice to a panel of compounds were studied (desflurane, isoflurane, and halothane in all cases; ethanol, the experimental anesthetic 1-chloro-1,2,2-trifluorocyclobutane [1A] and the nonimmobilizer 1,2-dichlorohexafluorocyclobutane [2N], for selected animals). We chose these compounds because they span a range from high to low polarity (from ethanol with a saline/gas partition coefficient of 2650 to 2N with a saline/gas partition coefficient of 0.0119), and include agents widely used clinically, as well as a volatile agent lacking immobilizing effects (2N) (6) and an experimental anesthetic structurally similar to the nonimmobilizer (1A). For the conventional anesthetics, ethanol and 1A, MAC was determined. For the nonimmobilizer, the convulsive 50% effective dose (ED₅₀) (the dose required to produce convulsions in 50% of animals) was measured.

	Methods

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With approval of our committee on animal research, we studied 207 male mice, several on repeated occasions: 24 C57BL/6 NHsd and 16 129/Ola Hsd mice (Harlan, Indianapolis, IN), 24 129/J, 16 DBA/2J, 24 B6129F2/J (a hybrid mouse derived from the C57BL/6 and 129/J strains), 16 129/SvJ, 24 C57BL/6J, 16 Mus musculus castaneus (Cast/Ei), 8 Mus spretus (Spret/Ei), and 16 PKC knockout mice (Jackson Laboratories, Bar Harbor, ME), and 23 Crl:CD-1 BR mice (Charles River, Hollister, CA). Animals were housed six to a cage in our animal-care facility for at least 1 wk before study, under 12-h cycles of light and dark. They had access to food and water ad libitum. Mice were 7 to 9 wk old.

MAC for halothane, desflurane, and isoflurane was determined in each mouse, with at least 1 wk separating each determination of MAC. A subgroup of animals had MAC for 1A (Lancaster Synthesis, Inc, Windham, NH) determined subsequently after MAC to the conventional agents had been established.

Eight B6129F2/J mice had the distal 0.5 cm of their tails clipped off after these MAC determinations and were allowed to recover for 2 wk, after which we redetermined MAC of desflurane, isoflurane, and halothane.

At the end of this portion of the study (in which the MAC of desflurane, isoflurane, and halothane was determined for each animal), 12 to 16 of the animals of selected strains were used to determine the MAC of ethanol. Four to eight of the remaining animals from among these strains were tested for convulsive ED₅₀ to 2N (PCR, Gainesville, FL). Animals were killed after these studies.

During the study, all animals were in individual plastic chambers connected to a circle system containing a CO₂ absorber, fan, and oxygen source, as described previously (7). Desflurane, isoflurane, halothane, 1A, and 2N were delivered using commercial anesthesia vaporizers. The temperature of each mouse was measured rectally and maintained between 36°C and 38°C using a heat lamp or application of ice bags to the plastic chambers as needed.

The anesthetic ED₅₀ (MAC) was measured for desflurane, isoflurane, and halothane as the mean of the partial pressures bracketing the animal’s response and lack of response to a 1-min tail clamp (2). If an animal responded to the tail clamp, the partial pressure of the inhaled drug was increased in steps of approximately 20% until no response was obtained. The animals breathed each anesthetic partial pressure for 20 min for desflurane, 30 min for isoflurane and 1A, and 40 min for halothane, to achieve tissue equilibration with the inspired anesthetic. For each strain, MAC was the average of the MAC for individual mice, each animal contributing one value. For CD-1 and C57BL/6J mice, MAC for 1A was determined by additivity with desflurane (8) because this compound was lethal in these strains at anesthetizing partial pressures.

To determine the MAC for ethanol, animals were injected intraperitoneally with various doses of 20% (volume/volume) ethanol solution in saline. Forty minutes later, the tail of the animal was clamped for 1 min. Movement, or absence of movement, was noted. To determine the ethanol partial pressure in the mouse, the brain of the animal was removed and placed in a 10-mL glass syringe containing air. The syringe and contents were equilibrated for 2 h at 37°C, and the ethanol partial pressure in the gas phase was analyzed by gas chromatography. Anesthetic ED₅₀ was calculated using logistic regression (9).

For 2N, we measured the convulsive ED₅₀ using a bracketing method as described previously (10). The partial pressure at which animals convulsed, averaged with the highest partial pressure at which the animals did not convulse, was taken as the convulsive ED₅₀. The partial pressure of 2N was increased in 20% steps until convulsions were seen.

One-way analysis of variance was performed for each agent, comparing the MAC values between strains. Post hoc multiple comparisons were done using the Student-Newman-Keuls test.

To determine whether PKC knockout mice had a different MAC for a given agent than the B6129F2/J, 129/Ola hsd, or C57BL/6J strains, a Mann-Whitney rank sum test was performed, with a Bonferroni correction for three comparisons. We used a binomial test to determine whether clipping the tails changed MAC.

We performed bivariate least squares linear regressions using MAC data for halothane, desflurane, and isoflurane to determine whether MAC for one agent predicted MAC for either of the other agents (i.e., whether the slope of the regression line for any two drugs was statistically significantly different from zero). P < 0.05 was considered significant.

	Results

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Although the differences were small, MAC and convulsivity differed significantly among strains (see Table 1). In general, 129/J mice had lower MAC values than most strains and the highest convulsive threshold, whereas Spret/Ei mice had higher MAC values. Cast/Ei mice tended to have high MAC values as well, but this did not reach statistical significance compared with most strains. Bivariate regression of MAC data for halothane, isoflurane, and desflurane showed that MAC for isoflurane predicted MAC for desflurane, but halothane MAC was not predictive of isoflurane or desflurane MAC (slope ± SE, for regression of desflurane MAC values on isoflurane MAC values was 0.157 ± 0.052, P = 0.016; for desflurane on halothane, 0.033 ± 0.031, P = 0.32; for isoflurane on halothane, 0.329 ± 0.795, P = 0.69).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
We studied the strain-related variability in MAC and convulsive ED₅₀ to provide a reference base for MAC and convulsivity results that might be obtained in studies of genetically modified animals. Because inbred strains are expected to differ in behavioral responses and in sensitivity to drugs (11), interpretation of the results of gene targeting studies requires a knowledge of the phenotype of the strains used to produce genetically altered animals (12). Strains 129 and C57BL/6 provide the background for many genetically modified mice. We accordingly studied several of these strains in this study. For comparison, we studied another subspecies (Cast/Ei) and species (Spret/Ei), and a hybrid and outbred strain of laboratory mice.

Our data indicate that strain differences modestly but significantly influence anesthetic potency (MAC) (Table 1). Differences for any given agent ranged from 17% to 39% from the lowest to highest values for MAC for conventional anesthetics and up to 48% using the experimental anesthetic 1A. Linear regression analysis of MAC data (excluding the PKC MAC data) showed that MAC of isoflurane was predictive of the MAC for desflurane, but neither isoflurane nor desflurane MAC correlated with halothane MAC (i.e., the slope of the regression lines did not differ significantly from zero). If this relation is retained as more strains are studied, it would be reasonable to conclude that there is a different genetic basis for the variation in MAC values between halothane and either desflurane or isoflurane.

The noted differences in MAC were largest between species of mouse studied (Spret versus laboratory strains). A comparison can be further made to rats (3) because the MAC of desflurane has been determined in five rat strains (Long-Evans, Sprague-Dawley, Wistar, Brown Norway, and Fischer). These MAC values ranged from 6.59% of an atmosphere (atm) to 8.33% atm. The absolute value and range of MAC values is thus similar in rats and mice (6.55% to 9.12% atm in this study), suggesting that the determinants of MAC may have been conserved over the several millions of years of evolution separating rats and mice from their common rodent ancestors.

Despite the smallness of the differences in MAC between strains, many differences were significant because of the smallness of the variability in the measures of potency. This permitted us to test whether MAC for a specific knockout strain differed from the MAC for control strains. We chose to study mice knocked out for the PKC gene because they show decreased sensitivity to ethanol as measured by loss of the righting reflex and the development of hypothermia (5). Other factors also made these mice attractive for study. Because the PKC gene is not expressed until seven days postnatally, the effect of the absence of this gene on the development of the central nervous system should be less than for genes expressed in utero. This should limit potentially confounding developmental compensations for absence of the gene. Although these mice have been found to have a mild impairment in spatial and contextual learning (13), mild ataxia (14), and reduced responses to neuropathic pain (15), in most regards they appear and behave normally.

As we predicted, PKC knockout animals had higher MAC values for isoflurane and desflurane than the control B6129F2/J, C57BL/6J, and 129 Ola Hsd mice (Table 1). These differences (22%–28% above control) reached statistical significance in all three strains in the case of isoflurane. However, PKC knockout mice do not have higher halothane MAC values than control animals. We conclude that protein phosphorylation by PKC can modulate sensitivity to the immobilizing effects of isoflurane and perhaps to desflurane, but not to halothane. The differences we see between anesthetics in these mice suggest differences in the genetic basis of anesthetic action in mice. This is consistent with results from studies in drosophila (16) and Caenorhabditis elegans (17), which indicate several genetic influences on anesthetic action.

Several caveats limit the interpretation of the results for the PKC mice. First, the issue of genetic background is especially important in this case because the regulation of protein phosphorylation is complex and not determined solely by the level of a single protein kinase isoform [see, for example, (18)]. To control for this, we compared MAC values in the knockout mice with MAC in the C57BL/6J and 129 Ola Hsd mice used in the creation of the knockout, and with the B6129F2/J hybrid strain. The hybrid mice are an important, though approximate, control for the genetic background of the PKC knockout mice because the PKC knockout colony is maintained homozygously, and, hence, there are no wild type litter mates with mixtures of C57BL/6 and 129 genes that can be used as controls.

The 129 and C57BL/6 controls are informative because the PKC knockout is produced by introducing a piece of chromosome carrying the disrupted PKC gene plus adjacent genes into 129 derived cells, rather than an isolated gene. As a result, the disrupted and wild type genes will be linked to genes from different mouse strains—for the knockout animal, genes derived from the 129 mouse subline will cosegregate with the disrupted PKC gene, whereas for the wild type animal, genes from C57BL/6 mice will cosegregate with the wild type PKC gene. These other unknown but linked genes might account for the differences between knockout and control strains (19). In our case, the fact that the knockout mice differ from the 129 Ola Hsd mice for isoflurane suggests that the increase in MAC for that agent is attributable to the knockout and not background genes.

Second, amputating the tip of the tail of genetically engineered mice to provide a tissue sample for genetic analysis might lead to sensitization of the spinal cord, with an enlargement of fields receptive to the input from stimulation of the tail, leading, thereby, to a hyperalgesic response to noxious stimuli (20). This might increase MAC. However, this was not the case, and thus spinal sensitization cannot account for the increase in MAC to isoflurane seen in PKC mice. The absence of a change in MAC for halothane also argues against a nonspecific increase in MAC resulting from spinal sensitization. PKC knockout mice also would seem unlikely to develop spinal sensitization because in a model of neuropathic pain using sciatic nerve sectioning (15), PKC mice had a reduced, not enhanced, development of neuropathic pain.

Third, the finding of a difference in MAC between control and knockout animals might simply be the result of an alteration in transmission of acute painful stimuli as a result of the knockout, rather than an effect at a site essential to the action of anesthetics. Because unanesthetized PKC knockout mice have normal thresholds to acute pain as assessed by paw withdrawal to thermal or mechanical stimulation (15), a change in processing of acutely painful stimuli is unlikely to explain the increase in MAC in these mice.

The convulsive ED₅₀ to 2N was highest in 129/J mice, and this strain had the lowest or second lowest values for MAC. Such a strain-related inverse relationship between MAC and convulsive ED₅₀ parallels that which we described previously in rats (3). We proposed that this might be related to the balance between the excitatory and depressant effects of each compound. However, such an opposing effect was not noted for other mouse strains.

In summary, we report statistically significant but modest differences in MAC values for three conventional anesthetics and ethanol among mouse strains and strain-related differences in the convulsive ED₅₀ for 2N. Amputating the tip of the tail did not affect MAC. We also report that PKC knockout mice are less sensitive to the immobilizing effect of isoflurane, a finding that suggests that protein phosphorylation by PKC can modulate this anesthetic’s sensitivity. The protein substrate that PKC phosphorylates to modulate the anesthetic effect of isoflurane is not known. Our results suggest the possibility that more than one gene may underlie the variability we observed in sensitivity to anesthetics.

	Acknowledgments

 
This work was supported in part by National Institutes of Health Grant 1P01GM47818–03.

	Footnotes

 
EIE II is a paid consultant to Baxter Pharmaceutical Products, Inc.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Homanics GE, Quinlan JJ, Mihalek RM, et al. Alcohol and anesthetic mechanisms in genetically engineered mice. Front Biosci 1998;3:548–58.
2. Quasha AL, Eger EI II, Tinker JH. Determination and applications of MAC. Anesthesiology 1980;53:315–34.[ISI][Medline]
3. Gong D, Fang Z, Ionescu P, et al. Rat strain minimally and reciprocally influences anesthetic and convulsant requirements of inhaled compounds in rats. Anesth Analg 1998;87:963–6.[Abstract/Free Full Text]
4. Koblin DD, Eger EI II. Cross-mating of mice selectively bred for resistance or susceptibility to nitrous oxide anesthesia: potencies of nitrous oxide in offspring. Anesth Analg 1981;60:646–8.[Abstract/Free Full Text]
5. Harris RA, McQuilkin SJ, Paylor R, et al. Mutant mice lacking the isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of -aminobutyrate type A receptors. Proc Natl Acad Sci USA 1995;92:3658–62.[Abstract/Free Full Text]
6. Eger EI II, Koblin D, Harris R, et al. Hypothesis: inhaled anesthetics produce immobility and amnesia by different mechanisms at different sites. Anesth Analg 1997;84:915–8.[ISI][Medline]
7. Sonner J, Li J, Eger EI. Desflurane and nitrous oxide, but not nonimmobilizers, affect nociceptive responses. Anesth Analg 1998;86:629–34.[Abstract]
8. Koblin D, Chortkoff B, Laster M, et al. Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis. Anesth Analg 1994;79:1043–8.[Abstract/Free Full Text]
9. Fang Z, Ionescu P, Chortkoff BS, et al. Anesthetic potencies of n-alkanols: results of additivity and solubility studies suggest a mechanism of action similar to that for conventional inhaled anesthetics. Analg 1997;84:1042–8.[Abstract]
10. Fang Z, Sonner J, Laster MJ, et al. Anesthetic and convulsant properties of aromatic compounds and cycloalkanes: implications for mechanisms of narcosis. Anesth Analg 1996;83:1097–104.[Abstract]
11. Phillips TJ. Behavior genetics of drug sensitization. Crit Rev Neurobiol 1997;11:21–33.[ISI][Medline]
12. Gerlai R. Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? Trends Neurosci 1996;19:177–81.[ISI][Medline]
13. Abeliovich A, Paylor R, Chen C, et al. PKC mutant mice exhibit mild deficits in spatial and contextual learning. Cell 1993;75:1263–71.[ISI][Medline]
14. Chen C, Kano M, Abeliovich A, et al. Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKC mutant mice. Cell 1995;83:1233–42.[ISI][Medline]
15. Malmberg AB, Chen C, Tonegawa S, et al. Preserved acute pain and reduced neuropathic pain in mice lacking PKC. Science 1997;278:279–83.[Abstract/Free Full Text]
16. Campbell D, Nash H. Use of drosophila mutants to distinguish among volatile general anesthetics. Proc Natl Acad Sci USA 1994;91:2135–9.[Abstract/Free Full Text]
17. Morgan P, Sedensky M. Mutations conferring new patterns of sensitivity to volatile anesthetics in Caenorhabditis elegans. Anesthesiology 1994;81:888–98.[ISI][Medline]
18. Cooper JR, Bloom FE, Roth RH. The biochemical basis of neuropharmacology. 7th ed. Oxford:Oxford University Press, 1996.
19. Lathe R. Mice, gene targeting and behaviour: more than just genetic background. Trends Neurosci 1996;19:183–6.[ISI][Medline]
20. Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature 1983;306:686–8.[Medline]

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999