Inter- and intrastrain variation in mouse critical
running speed
Veronique L. Billat, Etienne Mouisel, Natacha Roblot and Judith Melki
Journal of Applied Physiology 98:1258-1263, 2005. First published Nov 12, 2004;
doi:10.1152/japplphysiol.00991.2004
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J Appl Physiol 98: 1258 –1263, 2005.
First published November 12, 2004; doi:10.1152/japplphysiol.00991.2004.
Inter- and intrastrain variation in mouse critical running speed
Veronique L. Billat,1 Etienne Mouisel,1,2 Natacha Roblot,2 and Judith Melki2
1
Unité de Formation et de Recherche Fondamentale et Appliquée, Laboratory of Exercise
Physiology EA3872, and 2Molecular Neurogenetics Laboratory, Institut National
de la Santé et de la Recherche Médicale, E223, University of Evry, Evry, France
Submitted 9 September 2004; accepted in final form 5 November 2004
heritability; exercise
EXERCISE PROVIDES ONE OF THE most severe, yet physiological
stresses to the cardiovascular system and represents a major
determinant of the utilization of metabolic substrates. The
adaptations to exercise are the result of a coordinated response
of multiple organ systems, including cardiovascular, pulmonary, endocrine-metabolic, immunological, and skeletal muscle. With the generation of mouse models of human cardiovascular or neuromuscular diseases, the development of noninvasive methods represents an important goal toward an
accurate evaluation of physiological responses to stress (5).
In the present study, we investigated the possibility that
critical speed (CS), a well-recognized parameter of motor
performance in humans (32) and more recently in horses (26),
could be used to assess the aerobic capacity in mice. CS is
based on the hyperbolic relationship between speed and time to
fatigue for individuals during separate bouts of exhaustive runs
performed at different speeds (35). Therefore, the tolerable
duration of high-intensity exercise decreases hyperbolically as
a function of the speed. The CS is the y-axis asymptote of this
relationship and can be sustained theoretically to infinity but
experimentally between 40 and 60 min. This hyperbolic relationship between speed and time to exhaustion can be transformed to a linear relationship between distance run and time
to fatigue, according to the following equation linking the time
to cover a distance (d) (10, 32): d ⫽ ADC ⫹ CS ⫻ t, where t
Address for reprint requests and other correspondence: V. L. Billat,
Laboratory of Exercise Physiology , UFRSFA, Université d’Evry-Val
d’Essonne Boulevard François Mitterrand, 94025 Evry Cedex France
(E-mail: [email protected]).
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is the time to exhaustion (in seconds) at a given speed, CS is in
meters per second, and ADC is the so-called anaerobic distance
capacity, i.e., a finite quantity of distance (meters) that can be
covered above the CS by using energy derived from anaerobic
glycolysis, phosphate, and oxygen stores. Therefore, CS and
ADC are representative of the aerobic and anaerobic metabolisms, respectively (10, 32). Furthermore, the CS has been
shown to be the highest constant work rate that can be sustained without inexorably increasing O2 uptake (V̇O2), blood
lactate, and H⫹ (33). Genetic traits contribute to the aerobic
phenotype and to the adaptation to exercise (6, 7). In addition,
given the tight relationship between genetic and environmental
factors in the aerobic capacity, studying animal models carrying genetic modifications and submitted to minimal environmental variations could be of substantial value for identifying
the genetic components of aerobic capacity variability (8). The
CS determination does not require any invasive material and
could represent a valuable means for measuring motor performance enhancement after a training protocol or a medical
treatment in animal models.
The main purpose of this prospective study was to explore
the possibility of using the CS concept in a mouse model and
to evaluate inter- and intrastrain variability of CS, as well as a
sex effect. Therefore, this study examined two hypotheses: 1)
that critical running speed can be used as an indicator of
exercise performance, and 2) that different inbred mouse
strains differ in critical running speed after we checked the sex
effect in one strain (the C57 BL/6J).
MATERIALS AND METHODS
Animals. Four groups of 15 mice were tested: 3 groups of males of
different strains, CD1, FVB/N and C57BL/6J, and one group of
females of the C57BL/6J genetic background. Among each group,
seven mice performed the incremental test to determine the speed at
the lactate threshold [lactate threshold velocity (vLT)]. All mice were
purchased from Charles River (Charles River Laboratories,
L’Arbresle, France). Mice were maintained in our animal house in
pathogen-free environment, at 22°C with 12:12-h light-dark cycles,
and had water and food ad libitum (A03–10, SAFE, Villemoissonsur-orge, France). Mice were included into the training protocol at 8
wk of age. Fifteen males maintained on FVB/N, CD1, and C57BL/6J
genetic backgrounds and fifteen C57BL/6J females were analyzed.
FVB/N and CD1 were selected according to their high-performance
level in endurance exercises on the treadmill or wheel (27). C57BL/6J
was chosen because it is the most commonly used strain for genetic
and/or transgenic study. All animal procedures used in this study were
performed in accordance with institutional guidelines (agreement
numbers A91–228-2 and 3429).
The costs of publication of this article were defrayed in part by the payment
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in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Billat, Veronique L., Etienne Mouisel, Natacha Roblot, and
Judith Melki. Inter- and intrastrain variation in mouse critical running speed. J Appl Physiol 98: 1258 –1263, 2005. First published
November 12, 2004; doi:10.1152/japplphysiol.00991.2004.—With
the generation of mouse models of human cardiovascular or neuromuscular disorders, the development of noninvasive methods to evaluate the physiological responses to exercise presents an important
challenge. The possibility for determining critical speed (CS) in the
mouse model was examined according to strain (CD1, C57BL/6J,
FVB/N) and sex. Sixty mice performed four exhaustive runs on a
treadmill to determine their CS. Twenty-one performed an incremental test to determine the velocity at the lactate threshold. CS was
significantly different between the strains (P ⬍ 0.0001) but not
between sexes. Two measures of heritability showed that CS was
partially heritable. CS was not significantly different from lactate
threshold velocity. We conclude that CS, which reflects the aerobic
capacity, can be determined in mice, as in humans and horses.
Considering the intrastrain variability, CS could represent a valuable
means for designing an optimal and individualized physical training in
mice.
CRITICAL RUNNING SPEED IN MICE ACCORDING TO STRAIN
Fig. 2. Determination of velocity at the lactate threshold (vLT) in one mouse
(C57BL/6J male) on the treadmill, according to the protocol described in
MATERIALS AND METHODS. In this mouse, vLT is at 95% of the CS. [La], lactate
concentration; CV, coefficient of variation.
differences, post hoc Dunnett’s t-test was applied to evaluate intrastrain differences (2). For each parameter, the strain displaying the
lowest average value was compared with other strains to determine
which strain differed significantly from the lowest. Differences between sexes were evaluated in C57BL/6J genetic background using
Student’s t-test for nonpaired data (n ⫽ 7). Correlations between
lactate threshold and CS on one side and between CS and ADC on the
other side were evaluated using the Pearson correlation test. Results
are presented as means ⫾ SD. Statistical significance was set at P ⬍ 0.05.
Determination of heritability of the CS, lactate threshold speeds,
and anaerobic capacity was calculated by estimating broad-sense
heritability. Broad-sense heritability is usually considered as the
degree to which the phenotype is determined by the genotype (13).
Interclass correlations and the coefficient of genetic determination
(g2), two measures of heritability in the broad sense, were calculated
using methods outlined by Festing (15) and Falconer and Mackay (13)
and recently applied by Lightfoot et al. (28) to estimate the interstrain
variation in murine aerobic capacity. Intraclass correlations (rI) were
defined as the proportion of the total variation that was accounted for
by genetic differences between the strains, whereas the calculation of
the g2 provided a similar indication but corrects for the doubling of
genetic variance that occurs with inbreeding (15). The rI and g2 were
calculated as follows: rI ⫽ (MSB ⫺ MSW)/[MSB ⫹ (n ⫺ 1)MSW] and
g2 ⫽ (MSB ⫺ MSW)/[MSB ⫹ (2n ⫺ 1)MSW], where MSW and MSB
are the within- and between-strain mean square, respectively, i.e., the
mean square of the within- and between-strain comparison, and n is
the number of animals per strain (15, 27, 28).
RESULTS
Fig. 1. Determination of critical speed (CS) in one mouse (CD1) on the
treadmill, according to the protocol described in MATERIALS AND METHODS.
J Appl Physiol • VOL
Validation of critical running speed in mice. CS was determined in 60 mice belonging to FVB/N, CD1, and C57BL/6J
strains. The coefficient of determination (r2) of the distancetime running relationship was ⬎0.98, whatever the strain and
the sex (Table 1). As in humans and horses, the CS model is
reliable in mice, as the distance-time-to-exhaustion relationship follows a regression line not significantly different from
zero. To determine whether CS could be used to evaluate interor intravariation, this physiological parameter was evaluated in
three different genetic backgrounds using the same protocol.
Statistically significant lower CS was observed in C57BL/6J
mice (18.0 m/min) compared with either FVB/N (22.0 m/min)
or CD1 (24.1 m/min, P ⬍ 0.0001, Table 1) (Fig. 3). The CS of
the FVB/N and CD1 mice was not significantly different (P ⫽
0.15, n ⫽ 15). However, the ADC was not significantly
different between strains (P ⫽ 0.30). This could be due to the
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Evaluation of the CS. Mice were maintained in our animal house
for 1 mo before being included into the training protocol. The mice
ran on a 10.6 ⫻ 30-cm double-lane treadmill (LE 8709, Bioseb,
Chaville, France). A shock grid that delivered 0.2 mA was placed 10
cm from the rear of the cell to provide a stimulus to make the animals
run (28, 38). The protocol consisted of four runs leading to exhaustion, according to previous studies (9, 10). A single trial was performed per day, and the protocol covered a period of 4 days. Each trial
consisted of a run at constant speed. Four speeds were tested in each
mouse (18 –51 m/min). The time that the mice were able to run was
recorded at each speed and was arbitrarily limited to 45 min or
exhaustion, as defined by a total number of 50 shocks. Two parameters were used to estimate endurance performance: the distance (in
meters) the mice were able to cover at a given speed and the time to
cover the distance (limit time, seconds). The CS and ADC were
calculated, respectively, from the slope (a) and the intercept (b) of the
regression line, plotting the distance vs. the time to exhaustion from
the four tests, according to the equation y ⫽ ax ⫹ b (Fig. 1).
Incremental exercise test. This second test was performed to
determine the lactate threshold. Three days after the evaluation of CS,
mice performed an incremental test consisting of a starting speed of
70% of their CS for 3 min. Then a 5% increased speed was applied
every 3 min to reach a final speed of 120% of CS for 3 min. Each step
was separated by a 20-s rest. Blood lactate concentration was determined in a sample (5 ␮l) collected from the tip of the tail using a
lactate pro-LT device (Arkray, Kyoto, Japan). Blood was collected
before the onset of incremental test, during rest, and 2 min after the
end of exercise. The vLT was defined as the speed at which an
increase of ⬎1 mM occurred when lactate concentration was between
3.5 and 5 mmol/l. In humans, this range method of vLT determination
has previously been reported to estimate the maximal lactate steady
state in an incremental exercise protocol (1). Furthermore, in humans
and also in rats, it has been shown that the maximal blood lactate
concentration compatible with a lactate steady state was, in most of
the subjects and exercises, between 3 and 6 mM (1, 3, 4). Furthermore, given that, for most data collected, a decrease in blood lactate
was observed after the first increase, vLT was determined when blood
lactate criteria were observed without any further increase in blood
lactate concentration (Fig. 2).
Statistical analysis. The strain and sex effect on the CS was tested
in all mice (15 in each group), whereas the comparison between the
CS and the lactate threshold speeds was carried out on seven mice in
each group. Tests for statistically significant differences between
strains or sexes were performed, based on the assumption of the
normality and of the equality of the variance, using Sigmastat 2.03
software (SPSS). A one-way analysis of variance was performed to
test the strain effect. If analysis of variance indicated significant
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CRITICAL RUNNING SPEED IN MICE ACCORDING TO STRAIN
Table 1. Critical speed, anaerobic distance capacity, and determination coefficient of the relationship between distance run
and time to fatigue according to strain and sex of the mice
Variable
CD1 (Males)
C57BL/6J (Males)
FVB/N (Males)
C57/BL6J (Females)
Strain Effect P
Sex Effect P
CS, m/min
ADC, m
r2
24.1⫾4.6
37.2⫾25.7
0.985⫾0.023
18.0⫾1.5
45.9⫾21.8
0.988⫾0.015
22.1⫾2.8
35.5⫾16.8
0.994⫾0.011
17.8⫾2.7
39⫾23
0.986⫾0.020
⬍0.00001
0.99
0.32
0.74
0.40
0.79
Values are means ⫾ SD; n ⫽ 15 in each group. CS, critical speed; ADC, anaerobic distance capacity; r2, determination coefficient.
DISCUSSION
This study describes a procedure for the noninvasive measurement of exercise capacity in mice using critical running
speed as an approximation of lactate threshold for estimating
the aerobic capacity in humans, horses, rats, or mice (4). To our
knowledge, this is the first study demonstrating that the model
of CS can be applied in mice. The critical running speed is not
different between sexes for the C57BL/6J, the strain on which
this factor was tested. However, the CS differed significantly
between the strains, with the C57BL/6J and the CD1 being the
slowest and fastest strain, respectively. However, the intragroup variability of the CS showed that training speed and
duration must be individualized even within strain and sex.
Given the fact that mice represent an excellent genetic model
underlying exercise performance, this approach could provide
a valuable and easy-to-use tool for such studies.
The model of CS for the estimation of the aerobic capacity
in mice. The CS model can effectively be applied in mice
running on a treadmill. This study showed very high r2 values
(⬎0.98) when the simple polynomial expression (y ⫽ ax ⫹ b)
was used to determine CS from four tests. This value of r2 was
above those reported in some human studies (9, 10, 32). A true
linear relationship was found (and then r2 close to 1) when CS
is calculated with at least four trials, lasting between 1 min 30 s
and 20 min (9). We found that, in mice, this protocol should be
followed to avoid CS variability. The protocol of four trials
performed in 1 wk was compatible with the recovery ability of
the mice.
Taking into account these recommendations, we observed a
moderate coefficient of variation in each group (⬍10%), except for the FVB/N. However, we can consider that this
variability is nonnegligible in a group of animals having the
same genetic background and environment. Part of this variability can be explained by the aerobic characteristics of the
individual but is also probably related to some training problem. Indeed, some of the variability might be due to some of
the animals’ experienced training to the treadmill run until
exhaustion. Therefore, we observed that some C57BL/6J mice
reached the maximal number of shocks without being exhausted, suggesting that the conditioning was not efficient.
Therefore, the time that the mice were able to maintain the
intermediate speed did not increase as much as expected by
their time to exhaustion at higher speed. Such a problem did
not occur with CD1 mice. All CD1 displayed a high ability for
running on the treadmill. Nevertheless, the variability of the CS
Table 2. Lactate threshold speed and critical speed of the
mice according to their strain and sex (among
the C57/BL6J)
Fig. 3. The distance-time and CS (the slope of the regression line) in the 3
strains.
J Appl Physiol • VOL
Group
n
vLT, m/min
CS, m/min
P
CD1 (Males)
C57BL/6J (Males)
FVB/N (Males)
C57/BL6J (Females)
All mice
7
7
7
7
28
20.8⫾2.1
17.6⫾4.6
21.7⫾0.5
18.2⫾1.3
19.7⫾2.9
21.5⫾1.9
18.5⫾1.9
21.1⫾4.0
17.9⫾1.3
19.6⫾3.6
0.07
0.48
0.55
0.71
0.66
Values are means ⫾ SD; n, no. of mice, vLT, lactate threshold velocity.
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high variability of anaerobic distance within strain. Indeed,
ADC coefficient of variation was 63, 39, and 32% for the CD1,
FVB/N, and C57/BL6J, respectively. Regarding CS, the intravariability equaled 9, 19, and 10% for the CD1, FVB/N, and
C57/BL6J, respectively.
In contrast to the strain effect, there was no sex effect on CS,
ADC, and the determination coefficient of the distance runtime to fatigue relationship in the C57/BL6J. This strain was
the only one investigated for estimating the sex effect (Table
1). Two measures of heritability of the CS, i.e., the rI and the
g2, were both significant for CS (0.45 and 0.30, respectively)
but not for ADC (0.010 and 0.011, respectively).
The critical vs. the lactate threshold speed. The CS was also
not significantly different from the lactate threshold speed in all
mice (Table 2). Considering all of the mice (n ⫽ 60), ⬎70% of
the variance of the lactate threshold speed could be estimated
by the CS (Fig. 4). Blood lactate concentration at and above the
lactate threshold was significantly higher in the FVB/N mice
compared with C57BL/6J and CD1 (Fig. 5). In contrast, for the
C57/BL6J, there was no significant difference in blood concentration below, at, and above the lactate threshold between
sexes (blood lactate concentration at the lactate threshold was
3.8 ⫾ 0.7 vs. 4.3 ⫾ 0.4 mM for males and females, respectively, P ⫽ 0.11) (Fig. 5). These data indicate that CS could be
determined in mouse with tight correlation to vLT, a feature
similar to that found in humans (9, 11).
CRITICAL RUNNING SPEED IN MICE ACCORDING TO STRAIN
Fig. 4. Relationship between the CS and the vLT (n ⫽ 28). More than 70% of
the vLT variance can be predicted by the variance of the CS.
J Appl Physiol • VOL
blood lactate, lactate-to-pyruvate ratio, and H⫹ concentration
continue to rise (presumably reflecting intramuscular changes);
bicarbonate falls; and V̇O2 rises inexorably toward maximum
V̇O2 (V̇O2 max) (3, 4, 33). The CS is close to the lactate
threshold evaluated by determining blood lactate concentration
by using incremental, multistage treadmill exercise test to
determine the speed at the lactate threshold (3, 4, 9). We chose,
in the present study, this procedure, which has previously been
validated in horses (24, 43) and in rats (25, 42).
According to the reference values of V̇O2 max in mice (150 –
170 ml䡠 kg⫺1 䡠 min⫺1) and their energy cost of running (14, 36,
45), we can estimate that the CS in our untrained mice elicits
⬃75% of V̇O2 max. This figure is in accordance with the lack of
significant difference between the critical and the lactate
threshold speed, as previously reported in humans (9). These
results would offer a potential application of the mechanisms
for controlling exercise metabolism, as it has been recently
reported that mice mimic human responses to exercise after an
intensive interval training performed at 85–90% of V̇O2 max
(22, 45), which is the intensity range of the CS in humans (3,
4). Indeed, the adaptive response in the fast-twitch white fibers
began at 80% V̇O2 max and increased exponentially when intensity was increased. Therefore, CS could be a reference if the
target is to enhance the oxidative capacity of the type II fibers.
Indeed, the work rate associated with the lactate threshold
speed is considered as being an indicator of endurance exercise
capacity in humans and horses (24, 43) and in rats (25, 42).
The lactate threshold speed has been reported to be sensitive
to endurance training (3, 4, 43). Furthermore, the time to
exhaustion at the lactate threshold speed has recently been
reported to increase by 50% after training when V̇O2 max and
maximal lactate steady-state workload increased by only 5%
for V̇O2 max (3). Therefore, the CS, which takes into account the
time to exhaustion in a range of speeds between 70 and 120%
of V̇O2 max, has been reported in humans to be more sensitive
to training than the maximal V̇O2 or the speed at the lactate
threshold (44).
If the CS represents the aerobic capacity, ADC provides an
estimation of the energy to run faster than CS during a finite
time. This has been used in humans (10, 33) and in horses (26)
to estimate the anaerobic work capacity without the need for
Fig. 5. Strain and sex (for the C57BL/6J) effect on the blood [La] running at
speeds below, at, and above the vLT. The speeds are expressed as a percentage
of the CS. Values are means ⫾ SD. Open, shaded, and solid bars show the
average blood [La] at run speeds below, at, and above the vLT, respectively.
§
Significantly different from the C57BL/6J; ‡significantly different from the
FVB: P ⬍ 0.05.
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in the CD1 was only slightly less (8.9%) than that of C57BL/6J
(10.2%).
These data indicate that an individual calibration of intensity
and duration of training should be necessary, even in mice
belonging to the same strain. Furthermore, the measurement of
CS as an assessment of the aerobic capacity and a means for
training calibration in mice could offer an alternative to the
usual incremental exercise, which measured the total endurance time. On the treadmill, performance model and aerobic
capacity in mice are generally assessed by total exercise time
during an incremental speed or grade (12, 28). In the incremental test, the performance depends on the highest speed
reached by the animal, even for a short time. The first speed
stage of these standard incremental tests was the same whatever the strain (19.8 m/min) (27). Therefore, this protocol did
not take into account the interstrain variability. Indeed, the
speed (19.8 m/min) represents 78, 87, or 120% of the CS of the
CD1, FVB/N, and C57BL/6J found in our study, respectively.
In the same manner, the standard speed increments (1.5 m/min)
generally used in mouse exercise protocol also represent a
different relative speed (5–10%) of the CS, according to strain.
Exercise duration at a given speed has also been used to
estimate aerobic endurance capacity in mice (11). However,
the calculation of the CS from four trials allows a more
accurate evaluation of aerobic capacity than when based on a
single trial (3, 4).
This coefficient of variation is similar to that observed in
healthy and untrained humans (14) but much higher than in
studies performed in well-trained endurance subjects (8, 9).
The mice studied here were untrained, and the animals had
no wheel in their cages to allow spontaneous training, which
is reported to be efficient for improving aerobic capacity (19,
21, 38).
The determination of the CS could provide a reference for
better estimating the exercise input in mice, and CS could
indeed be more consistent in further studies in the assessments
of the effects (especially at a molecular level in animals) of
training. Indeed, the nature of fatigue (i.e., failure to sustain a
required power output) and training response will be influenced
by the type of exercise, its intensity, and duration (10). In
humans, it has been clearly shown that the CS delineates the
so-called “severe-intensity” domain (33) at which no gas exchange or metabolic steady state can be achieved. Rather,
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CRITICAL RUNNING SPEED IN MICE ACCORDING TO STRAIN
J Appl Physiol • VOL
number of beam breaks per minute during a 30-min treadmill
run at 19.8 m/min compared with all of the other strains,
whereas the CD1 and FVB/N had the lowest number (27). This
method for measuring the endurance of the mice did not take
into account the fact that the mice did not run at the same
percentage of their maximal speed (90% for the C57BL/6J vs.
48.5% for the FVB/N). In this study, the endurance test
consisted of four independent trials for the CS determination.
This endurance test was then maximal for all of the strains in
the same conditions of stress (50 electric shocks). Therefore,
this endurance test could be used to recalculate training exercise intensity with respect to the endurance and speed variability between and within strains. The CS integrates the speed and
time duration difference between individuals and strains. However, the C57BL/6J consistently showed the highest level of
voluntary wheel-running, not only for the duration (hours of
running by night), but also by the average speed and the
distance run. The second-best strain was the CD1, and far
behind was the FVB/N. These authors concluded that an
animal’s performance under forced exercise conditions does
not necessarily predict how that animal will perform in a
voluntary setting. We have to add that the endurance test was
not performed at the same relative exercise intensity, according
to the strain, as discussed previously, and that the ergometer
was not the same. A voluntary exercise model on a nonmotorized treadmill has not yet been reported.
Broad-sense heritability estimates for CS were rI ⫽ 0.45 and
g2 ⫽ 0.30, which were of same order as the voluntary wheelrunning duration performance and distance run (27, 38), maximal speed in horses (16, 17, 20, 34), and CS in horses (X.
Quilliet and V. L. Billat unpublished observations). Furthermore, even if this exercise model is successfully used for
selective breeding (21), this selection could be more based on
the behavior than on endurance capacity (18, 29, 37, 39). We
may suggest that the CS could also be a method of improving
the effectiveness of selective breeding, with the purpose of
improving aerobic capacity.
Conclusion. The present study shows that it may be possible
to determine, as in humans and horses, a CS, as the distancetime-to-exhaustion relationship follows a regression line not
significantly different than zero. The CS is not significantly
different from the blood lactate threshold speed at an intensity
that was estimated to be 75% of V̇O2 max, according to the
standard value of running economy and V̇O2 max reported in
untrained mice by Kemi et al. (22). This does not change,
whatever the strain and sex. Furthermore, the CS has a g2 of
0.40, which is similar to that obtained from a voluntary
wheel-running test. We can suggest that the CS could be a
means of selective breeding and training calibration to individualize the treadmill running intensity, even within a strain.
Therefore, the CS determination in mice of different strains
could represent a relevant means of measuring the performance
enhancement and of estimating modification of aerobic and
anaerobic metabolisms, after a training protocol or medical
treatment in mouse models. Because mice are an excellent
genetic and transgenic model for studying the molecular biology and genetics of exercise performance and adaptation, this
noninvasive approach has obvious value to the exercise research community.
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measuring the oxygen deficit, which is materially much more
difficult, especially in horses. This ADC has, however, a great
variability within mice of the same strain (30 – 40%). This is
rather surprising as the mouse is an animal that has a naturally
high percentage of fast fiber type, and we expected a more
homogeneous anaerobic work capacity. Therefore, if the measurement of the CS was satisfactory, the ADC associated with
this model (i.e., the intercept on the y-axis) should be an
artifact of the slope (i.e., the CS) and should be interpreted with
caution and compared with the oxygen deficit measurement (3,
4). The difference in performance between mice belonging to
the same strain could be attributed as much to the anaerobic
capacity as the aerobic capacity. ADC was between 35 and
46 m, according to the strain, but with a very high intragroup
variability. These results indicate that ADC was not a reliable
criterion to assess the anaerobic capacity, ADC, as previously
reported in humans or horses. Oxygen deficit should represent
a more valuable tool to evaluate the anaerobic metabolism.
Further studies are, however, required to explore the possible
relationship between the oxygen deficit assessing the anaerobic
work capacity and the ADC in mice (10, 30).
The CS variability in mice according to the strain and the
sex. The CS reflects the aerobic capacity, which is a complex
trait determined by the multifactorial interplay between genetic
and environmental factors. It is widely accepted that an individual’s traits depend on both genetic background and environmental factors (31). Given the complexity, the creation of
animal models in which both genetic and environmental variations approach minimums can be of substantial value (41).
The laboratory mouse model allows an investigation on how
the genetic influences phenotypic differences, such as the
training responsiveness (40). Up to now, the molecular mechanisms of adaptative cardiac and muscle modification in response to physiological stimuli remain virtually unexplored
because of a paucity of effective and well-controlled experimental models in this species. The only study using intensity
controlled treadmill running in mice instead of the voluntary
exercise regimen with little control of exercise intensity, and
the individual’s fitness level has recently been performed in
mice C57BL/6J of both sexes (22). This study was very
effective in the improvement of ventricular weight, V̇O2 max,
running economy (i.e., the energy spent by unit of body mass
and meter run), and skeletal muscle mass (22). The individualized intensity training for mice is promising, but, in this
previous study, the training intensity was calibrated in reference to V̇O2 max, which requires a rather sophisticated and
expensive protocol.
The present study addressed the possibility of determining a
CS for mice running on a treadmill in a perspective of aerobic
capacity assessment and of exercise intensity reference. For
that, we checked that the CS had a greater significant difference between than within strains. We chose to compare the
C57BL/6J, widely used as a biomedical model (27, 40), with
the other two strains, the FVB/N and CD1 chosen for their high
ability to run (27). The CS of the C57BL/6J was significantly
lower than those of the CD1 and FVB/N. This is in accordance
with the study by Lerman et al. (27), which showed that
C57BL/6J demonstrated the lowest maximum speed of all six
other strains determined in an incremental speed protocol (22.2
vs. 40.8 m/min for the FVB/N strain, which was the fastest).
Logically, the C57BL/6J demonstrated a significantly greater
CRITICAL RUNNING SPEED IN MICE ACCORDING TO STRAIN
GRANTS
This study was supported by grants from the Fondation d’Entreprise Gaz de
France and Genopole to V. L. Billat and from Institut National de la Santé et
de la Recherche Médicale, University of Evry, and the Fondation Bettancourt
Schueller to J. Melki.
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