Neuroscience 164 (2009) 1477–1483
VARIATIONS IN VENTRAL ROOT AXON MORPHOLOGY AND
LOCOMOTOR BEHAVIOR COMPONENTS ACROSS DIFFERENT
INBRED STRAINS OF MICE
J. G. DE MOOIJ-VAN MALSEN,a K. L. YU,a
H. VELDMAN,b H. OPPELAAR,a L. H. VAN DEN BERG,b
B. OLIVIERa,c,d AND M. J. H. KASa*
a
Rudolf Magnus Institute of Neuroscience, Department of Neuro-
science and Pharmacology, University Medical Center Utrecht, Utre-
cht, The Netherlands
b
Rudolf Magnus Institute of Neuroscience, Department of Neurology,
University Medical Center Utrecht, Utrecht, The Netherlands
c
Department of Psychopharmacology, Utrecht Institute for Pharma-
ceutical Sciences, Utrecht University, Utrecht, The Netherlands
d
Department of Psychiatry, Yale University School of Medicine, New
Haven, USA
Abstract—Locomotion is a complex behavior affected by
many different brain- and spinal cord systems, as well as by
variations in the peripheral nervous system. Recently, we
found increased gene expression for EphA4, a gene intri-
cately involved in motor neuron development, between high-
active parental strain C57BL/6J and the low-active chromo-
some substitution strain 1 (CSS1). CSS1 mice carry chromo-
some 1 from A/J mice in a C57BL/6J genetic background,
allowing localization of quantitative trait loci (QTL) on chro-
mosome 1. To find out whether differences in motor neuron
anatomy, possibly related to the changes in EphA4 expres-
sion, are involved in the motor activity differences observed
in these strains, motor performance in various behavioral
paradigms and anatomical differences in the ventral roots
were investigated. To correlate the behavioral profiles to the
spinal motor neuron morphology, not only CSS1 and its pa-
rental strains C57BL/6J (host) and A/J (donor) were exam-
ined, but also a set of other mouse inbred strains (AKR/J,
129ⴛ1/SvJ and DBA/2J). Significant differences were found
between inbred strains on home cage motor activity levels,
the beam balance test, grip test performance, and on alter-
nating versus synchronous hind limb movement (hind limb
hopping). Also, considerable differences were found in spinal
motor neuron morphology, with A/J and CSS1 showing
smaller, possibly less developed, motor neuron axons com-
pared to all other inbred strains. For CSS1 and C57BL/6J,
only genetically different for chromosome 1, a correlation
was found between motor activity levels, synchronous hind
limb movement and neuro-anatomical differences in spinal
motor neurons. Inclusion of the other inbred strains, how-
ever, did not show this direct correlation. These data verifies
the complex nature of the mammalian motor system that may
be further dissected using genetic mapping populations de-
rived from these inbred strains. © 2009 IBRO. Published by
Elsevier Ltd. All rights reserved.
*Corresponding author. Tel: ⫹31-88-756-8179; fax: ⫹31-88-756-9032.
E-mail address: m.j.h.kas@umcutrecht.nl (M. J. H. Kas).
Abbreviations: CSS, chromosome substitution strains; PFA, parafor-
maldehyde; QTL, quantitative trait loci.
0306-4522/09 $ - see front matter © 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.neuroscience.2009.09.008
1477
Key words: motor activity levels, motor neuron anatomy, ven-
tral roots, mouse, home cage, chromosome substitution strain.
For many years, differences in motor activity levels be-
tween inbred strains of mice have been subject to research
(Bothe et al., 2005; Cabib et al., 2002; Mhyre et al., 2005;
Tang et al., 2002). As locomotor activity is required for
many complex behavioral tasks, variation in activity non-
specifically affects performance in many behavioral tests
and can even function as a confounding factor (Kas et al.,
2004). The question rises to what extend this naturally
occurring variation in motor activity levels is caused by
changes on the (neuro⫺) anatomical level, emotional level
or, most likely, a combination of these two, and what this
implies for the validity of behavioural tests.
In a forward genetic screen using chromosome substi-
tution strains (CSS) on mouse behavioural traits, we re-
cently identified a quantitative trait loci (QTL) on chromo-
some 1 regulating motor activity levels in mice (Kas et al.,
2009). CSS mice allow systematic testing of single chro-
mosomes (here from A/J mice) in a controlled genetic
background (here from C57BL/6J) for their contribution
to complex traits. Genome-wide microarray gene expres-
sion profiling in brains of F2-individuals resulting from a
cross between C57BL/6J and chromosome substitution
strain 1 (CSS1) showed a significant upregulation of
EphA4 mRNA levels in the hippocampus of low active
F2-individuals. Further genetic analysis showed that
EphA4 may be an important signaling molecule in the
regulation of motor activity levels. This has also been
supported in recent studies using EphA4 mutant mice.
Locomotion is a complex behavior affected by many dif-
ferent brain- and spinal cord systems, as well as by variations
in the peripheral nervous system (Lemon, 2008; Lemon and
Griffiths, 2005). However, the exact underlying mechanisms
in which molecular and developmental changes within the
cortico-spinal tract affect behavior are largely unknown due to
its composite nature. For example, nitric oxide has been
found to modulate motor behavior both in essential brain
systems involved in emotion and locomotion (e.g. by interfer-
ing with neurotransmission in the striatum (Del Bel et al.,
2005)), as well as by influencing the molecular maturation of
motor neurons in the spinal cord (Kalb and Agostini, 1993).
This indicates that effects on the cortico-spinal tract should be
taken into account when examining the effect of, for instance,
genetic variations involved in motor activity levels. For exam-
ple, EphA4 has been found to be a crucial component in the
neuronal circuitry controlling movement due to its regulating
1478 J. G. de Mooij-van Malsen et al. / Neuroscience 164 (2009) 1477–1483
function in axon guidance and cell migration in the developing
(central) nervous system (Coonan et al., 2001; Kullander et
al., 2001). Additionally, EphA4-positive neurons are found to
be key components of the mammalian central pattern gener-
ators (Kullander et al., 2003) central pattern generators
(CPGs; the local circuits in the spinal cord responsible for
coordinated bilateral control over the normal limb alternation
that underlies walking). Also, Dottori et al., 1998 showed that
mice with a null mutation in the EphA4 gene displayed major
disruptions of the cortico-spinal tract. Consequently, homozy-
gous EphA4 knock out mice display extreme motor dysfunc-
tions, resulting in reduced and uncoordinated locomotor per-
formance (Kullander et al., 2003; Dottori et al., 1998; Helm-
bacher et al., 2000). Even though the CSS1 strain in general
displays a normal walking pattern, this does raise the ques-
tion whether this genetic background, possibly exerting its
effects on the nervous system during development as well as
adulthood, could contribute to the reduced motor activity lev-
els displayed by this strain and/or other inbred strains of mice.
To find out whether differences in motor neuron anat-
omy, possibly related to the changes found in EphA4 ex-
pression between CSS1 and C57BL/6J, are associated
with locomotor behavior differences observed in these
strains, motor performance in various behavioral para-
digms and anatomical differences in the ventral roots were
investigated. To correlate the behavioral profiles to the
spinal motor neuron morphology, not only CSS1 and its
parental strains C57BL/6J (host) and A/J (donor) were
examined, but also a set of other mouse inbred strains
(AKR/J, 129⫻1/SvJ and DBA/2J). The animals were
tested in a home cage environment allowing automated
longitudinal monitoring of motor activity levels (Kas et al.,
2008). Additionally, the animals were trained to perform on
a beam balance and grip test to examine muscle strength
and motor coordination. Further, the ventral roots of these
animals, containing motor neuron axons, were studied to
identify neuro-anatomical changes in this part of the motor-
circuitry as a function of genetic background.
EXPERIMENTAL PROCEDURES
Animals and husbandry
Male C57BL/6J (n⫽8), DBA/2J (n⫽8), AKR/J (n⫽8), 129⫻1/SvJ
(n⫽8), C57BL/6J-Chr1A/NaJ (simplified to CSS1) (n⫽7) and A/J
(n⫽6) mice were used. AKR/J and 129⫻1/SvJ males were obtained
from The Jackson Laboratory (Bar Harbor, ME, USA). For C57BL/6J,
DBA/2J, A/J and CSS1, initial breeding pairs were obtained from The
Jackson Laboratory (Bar Harbor, ME, USA) and animals bred from
our internal breeding program were tested. Mice were group housed
(2– 4 animals/cage; Macrolon type II; no. 1284 L) with food and water
available ad libitum, in a room maintained on a 12:12 h dark–light
cycle (white light on: 2:00 –14:00) and room temperature was main-
tained at 22.0⫾2.0 °C. Experiments were conducted when the mice
were aged 5–7 months old. Behavioral tests were conducted in a set
order (home cage environment; beam balance; grip test), with a
minimum of 1 week between tests.
For the eight mouse strains comparison for horizontal dis-
tance moved in the home cage, the data for the CSS1 and
C57BL/6J strain was derived from a subgroup of a previous study
(Kas et al., 2009). All experiments were approved by the Animal
Ethics Committee of Utrecht University and were conducted in
agreement with Dutch laws (Wet op de Dierproeven, 1996) and
European regulations (Guideline 86/609/EEC). In the design of
our experiments we have tried to minimize the number of animals
used and their suffering.
Home cage environment
For a description of the home cage environment dimensions, please
see Kas et al (2008). One hour prior to the start of the dark phase,
mice were weighed and placed individually in a home cage environ-
ment for 73 h. No experimenter interference took place during these
3 days. The distance moved, enter frequency and duration spent in
the shelter and on the two feeding platforms were obtained using the
video-tracking system (PhenoTyper® PT10S/P/N Version 1.01, Nol-
dus Information Technology, Wageningen, The Netherlands). The
PhenoTyper is a video-based observation system for automated
monitoring of rodent behavior. Integrated with the Ethovision® (Nol-
dus Information Technology, Wageningen, The Netherlands) video
tracking system, mice can be monitored automatically for several
consecutive days (de Visser et al., 2006). The top-unit contains an
infrared-sensitive CMOS camera and an array of infrared light-emit-
ting diodes and is connected to a computer running the EthoVision®
3.0 video-tracking software. Infrared sensors placed in front of the
food and water supplies registered the frequency and duration of
feeding and drinking. Data were analyzed for the first hour of testing
(novelty) and for the following days per 24 h.
Beam balance
The beam balance task is designed to analyze the vestibular-
motor coordination of the mice. The beam-balance apparatus is
composed of a circular platform (7 cm in diameter) and a narrow
beam (1.5 cm in width; 27.5 cm in length) which is connected to a
box (12.7⫻11.2⫻10 cm3). Lighting was provided by a desk light
(illumination level at 400 lux). The task was performed during the
dark phase of the circadian cycle. Mice were adapted to the test
room 15 min prior to the task. Animals were allowed to train once
a day for 4 days, followed by a test day. The maximum trial duration
was set to 10 min. At the start of each session the mouse was placed
at the circular platform. The latencies of exploring on the start plat-
form and crossing the beam to reach the covered box were recorded.
Between sessions, the apparatus was cleaned with 70% ethanol.
Grip test
The grip test was used to determine the muscle strength of the limbs
of the mice. Mice were tested on a grid (22⫻28.5 cm2) with a gap
width of 1 cm. The task was performed during the dark phase of the
circadian cycle. Animals were allowed to train once a day for 4 days,
followed by a test day. The task consisted of 5 min of testing, during
which the animal was hanging on the inverted grid with its fore-limbs
and hind-limbs (illumination level 130 lux). Mice that were able to hold
on for 5 min were considered to have passed the test. In between test
sessions, the grid was cleaned with 70% ethanol. On the test day, the
motor performance of each mouse was recorded on videotape and
further analyzed using Observer® (version 3.0, Noldus Information
Technology, The Netherlands). The frequencies of alternating hind
limb movement and hopping (synchronous) hind limb movement
were analyzed.
Tissue processing
Male mice of 7– 8 months old were anesthetized with pentobarbital
intra-peritoneally. Phosphate-buffered saline (PBS) with heparin was
infused intra-cardially. The animals were then perfused with freshly
prepared 4% paraformaldehyde (PFA; pH 7.30) and post fixed over-
night in 0.4% PFA at 4 °C until dissection. The ventral roots (left and
right) exiting the spinal cord at L4 were isolated. The ventral roots,
composed of axons originating from the motor neurons in the L4
spinal cord, were stored in 0.4% PFA, and then post fixed in 2%
 J. G. de Mooij-van Malsen et al. / Neuroscience 164 (2009) 1477–1483
osmium tetroxide, dehydrated in serially increasing concentration of
acetone and in Epon-acetone mixture overnight. Finally the ventral
roots were embedded in Epon resin, cut into 1 ␮m-thick sections with
a pyramitome (LKB. Ltd, Sweden) and stained with Toluidine Blue for
light microscopic examination. Per ventral root, three—four sections
were examined. Total root size was examined with a 10x magnifica-
tion; close-up analysis was performed by taking three randomly
chosen, non-overlapping fields within the root (Fig. 3A) with a 100x
magnification. Micrographs were taken with a digital camera, the size
and number of myelinated fibers was analyzed with ImageJ (http://
rsb.info.nih.go/ij; developed by Wayne Rasband, National Institute of
Mental Health, Bethesda, MD, USA).
Statistical analysis
All data are expressed as mean⫾ standard error of means (SEM)
unless indicated differently. Data were analyzed using SPSS 12
for Windows. Behavioral measurements and ventral root data
were analyzed using a one-way analysis of variance with Bonfer-
roni post hoc analysis.
RESULTS
Home cage environment
Home cage motor activity levels (horizontal distance moved)
(Fig. 1A, B) differed between inbred strains both during
baseline conditions (3rd day of testing; df⫽5; F⫽22.1;
P⬍0.001), as well as under novelty conditions (first hour of
testing; df⫽5; F⫽23.0; P⬍0.001). Rank order (from low to
high active) for distance moved baseline CSS1, 129⫻1/
SvJ⬍C57BL/6J⬍A/J, DBA/2J, AKR/J; rank order (from low
to high active) for novelty-induced distance moved A/J,
129⫻1/SvJ⬍CSS1, AKR/J, DBA/2J, C57BL/6J (with ⬍
indicating a significant strain difference with P⬍0.05).
Beam balance
All inbred strains were able to perform the beam balance
task (Fig. 1C). Traveling time across the beam was log-
transformed to fit a normal distribution. There was a sig-
nificant effect on traveling time (seconds) across the beam
(df⫽5; F⫽3.5; P⫽0.013). Post hoc analysis showed a
significant strain difference between C57BL/6J and 129⫻1/
SvJ on travel duration (P⫽0.015).
Grip test
A significant difference in grip duration was found (df⫽5;
F⫽6.2; P⬍0.001), with A/J, AKR/J and DBA/2J mice not
able to hold on the grid for the full 5 min of testing (Fig. 1D).
Rank order for grip duration is AKR/J, DBA/2J⬍A/J,
C57BL/6J, CSS1, 129⫻1/SvJ (with ⬍ indicating a signifi-
cant difference with P⬍0.05).
During the test, animals were initially hanging on the
inverted grid, but after some time started moving around
the grid. During this movement, significant differences in
the absolute frequency (df⫽5; F⫽12.0; P⬍0.001; Fig. 1E)
and percentage (df⫽5; F⫽13.0; P⬍0.001; Fig. 1F) of syn-
chronous hind limb movement (hind limb hopping) were
found, with CSS1 showing significant increase in hind limb
hopping frequency compared to the other strains. Rank
order for synchronous movement frequency A/J, 129⫻1/
SvJ, C57BL/6J, DBA/2J, AKR/J⬍CSS1 (with ⬍ indicating
1479
a significant difference with P⬍0.05); rank order for syn-
chronous movement percentage A/J, 129⫻1/SvJ,
C57BL/6J⬍AKR/J, CSS1, DBA2J (with ⬍ indicating a sig-
nificant difference with P⬍0.05).
Ventral root neuro-anatomy
In Fig. 2, representative pictures for close-up analysis of
the ventral roots are shown (randomly chosen field within
the ventral root). Clear differences are seen between the
inbred strains on axon morphology. Noteworthy is that
129⫻1/SvJ shows quite a different picture than the other
strains. As all ventral roots of all 129⫻1/SvJ animals
showed this phenotype, this is unlikely to be a fixation
effect. When examining the distributions of axon size
within the ventral roots (Fig. 2), it is clear that CSS1 and
A/J mice show a distribution very different from the other
strains. No axons larger than 80 ␮m2 are present within the
CSS1 and A/J ventral roots. For analysis, all axon sizes
were divided into bins of 50 ␮m2 (Fig. 3E). Significant
effects between strains were found for all bins (Bin0-50,
df⫽5; F⫽21.0; P⬍0.001; Bin50-100, df⫽5; F⫽11.4; P⬍
0.001; Bin100-150, df⫽5; F⫽34.6; P⬍0.001).
Total root size
Due to technical issues DBA/2J images of the total roots
were of insufficient quality to be included in this analysis.
Differences were found in the total size (cross section,
square micrometre) of the ventral roots (Fig. 3B; df⫽4;
F⫽18.3; P⬍0.001). Rank order for total ventral root size
129⫻1/SvJ, A/J, CSS1, AKR/J⬍C57BL/6J (with ⬍ indicating
a significant difference with P⬍0.05).
Number of axons per root
The number of axons per close-up picture were deter-
mined and multiplied by the total root area to calculate the
number of axons per root (Fig. 3C). A significant difference
was found in the total number of axons per ventral root
(df⫽4; F⫽7.0; P⫽0.001). Rank order for number of axons
per root C57BL/6J, AKR/J, 129⫻1/SvJ⬍CSS1, A/J (with ⬍
indicating a significant difference with P⬍0.05).
Axon size
A significant difference was found in the median axon size
between the inbred strains (Fig. 3D; df⫽5; F⫽26,1;
P⬍0.001). Rank order for median axon size 129⫻1/SvJ,
DBA/2J, A/J⬍CSS1, AKR/J⬍C57BL/6J (with ⬍ indicating
a significant difference with P⬍0.05).
DISCUSSION
In a forward genetic screen using CSS of mice, combined
with microarray expression data, we recently identified
EphA4 as a possible downstream target influencing loco-
motor activity levels. This is consistent with the known
function of this gene in the development of the neuronal
circuitry that controls locomotor behavior (Coonan et al.,
2001; Kullander et al., 2001, 2003; Dottori et al., 1998;
Goldshmit et al., 2004). In the present study, further motor
1480 J. G. de Mooij-van Malsen et al. / Neuroscience 164 (2009) 1477–1483

Fig. 1. Behavioral measurements for the inbred strains in the home cage environment, beam balance and grip test. Please see text for statistical
analysis. (A) Baseline motor activity levels on the third day of testing in the home cage environment. (B) Novelty induced motor activity levels during
the first hour of testing in the home cage environment. (C) Beam balance performance of inbred strains; average traveling time (s) across the beam
to reach the covered box. (D) Grip test performance of inbred strains; duration (s) the animals were able to hold on to the grid without falling (maximum
duration 300 s). (E) Frequency of synchronous (hind limb hopping) and alternating hind limbmovementlimb movement during the grip test of inbred
strains. (F) Percentage of synchronous (hind limb hopping) and alternating hind limb movement during the grip test of inbred strains.

functioning and neuro-anatomical data were collected on differences were found between the inbred strains on mo-
several inbred strains to explore possible correlations be- tor activity levels (horizontal distance moved), beam bal-
tween these parameters. Significant locomotor behavior ance and grip test performance, as well as on alternating
 J. G. de Mooij-van Malsen et al. / Neuroscience 164 (2009) 1477–1483 1481

Fig. 2. Inbred strains show morphological differences in L4 ventral roots anatomy. Representative images of semi-thin sections of the ventral root (A–F) are
shown for different inbred strains of mice. The number of axons (y-axis) per size-bin (␮m2; x-axis) are is displayed. Microscope images (100x) of ventral roots:
bar⫽10 ␮m. For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.

versus synchronous hind limb movement. Also, significant
differences in the neuro-anatomy of motor neuron ventral
root axons were found. However, no direct correlations
between locomotor behavior and ventral root neuro-anat-
omy were identified using a range of inbred strains.
When tested in the home cage environment, the selected
inbred strains show significant differences in motor activity
levels. Interestingly, under baseline conditions C57BL/6J
males show lower activity levels (horizontal distance moved)
than A/J. In a recent report on home cage distance moved
assessment across inbred strains of mice, Mhyre and co-
workers (2005) found the same rank order of motor activity
levels within these strains as in the present study. However,
in contrast to the present study, Mhyre et al. (2005) found that
C57BL/6J showed the highest motor activity levels after 3
days of testing. This may be explained by the way that home
cage motor activity levels were measured over several con-
secutive days. In the present study, motor activity levels were
assessed continuously over three consecutive days,
whereas Mhyre et al. (2005) performed separate measure-
ments for 45 min on three subsequent days; thus placing the
animals in the home cage on three occasions. As we find that
C57BL/6J expressed very high levels of novelty-induced mo-
tor activity levels, the procedural difference between the two
studies (continuous home cage measurements vs. three sep-
arate cage exposures) may explain the rank order position in
the two studies for C57BL/6J.
In all behavioral tests, 129⫻1/SvJ consistently exhibited
the lowest motor activity levels. Even though this strain is able
to perform the grip test, it shows the lowest level of movement
1482 J. G. de Mooij-van Malsen et al. / Neuroscience 164 (2009) 1477–1483

Fig. 3. Significant neuro-anatomical differences in ventral root and axon morphology. Please see text for statistical analysis. (A) A representative
image of ventral root with location of close-up images used for analysis shown in grey boxes. (B) Total size of the ventral root for several inbred strains.
(C) Number of axons present per ventral root for several inbred strains. (D) Median axon size in ventral root for several inbred strains. (E) Percentage
of axons per size-bin (␮m2) show significant differences between inbred strains. For interpretation of the references to color in this figure legend, the
reader is referred to the Web version of this article.

on the grid during the test. CSS1, AKR/J and DBA/2J display
a high level of synchronous “hopping” hind limb movement.
The alternated or “hopping” movement pattern of these
strains does not directly correlate with the ability to perform
the grip test, as CSS1, contrary to AKR/J and DBA/2J, is able
to finish the grip test for 5 min. Interestingly, this high-hopping
phenotype of CSS1 compared to C57BL/6J is consistent with
that observed in EphA4 knock out mice (Akay et al., 2006),
for which it is indicated to be a form of uncoordinated move-
ment. Under baseline conditions, CSS1 does not display this
synchronous movement pattern. Possibly, this is due to a
subtle dysfunction within this system which only behaviorally
expresses itself when higher workload is applied to the
muscles.
Interestingly, CSS 1 mice showed a different behavioral
phenotype when compared to both founder strains A/J and
 J. G. de Mooij-van Malsen et al. / Neuroscience 164 (2009) 1477–1483
C57BL/6J. This suggests the presence of transgressive seg-
regation across the progeny, a phenomenon characterized
by the emergence of new or extreme phenotypes in segre-
gating hybrid populations when compared to parental strains
(Kas et al., 2009; Rieseberg et al., 1999; deVicente et al.,
1993). Transgressive segregation can be explained by the
complementary actions of additive alleles that are amplifying
and attenuating the trait and dispersed at different loci in the
parental strain (Rieseberg et al., 1999). In such a case, there
can be a combination of more increasing alleles among the
offspring than found in either parent, leading to the emer-
gence of transgressive phenotypes (Rieseberg et al., 1999).
To further obtain insights into the neuron anatomy, ven-
tral roots from the L4 spinal region were collected and exam-
ined for differences in axon-anatomy. These studies demon-
strate large differences in the morphology of the ventral roots
between different inbred strains, both in size and number of
axons present. Intriguingly, CSS1 and AJ appear to have
smaller axons than C57BL/6J and the other inbred strains
examined. No large axons (⬎100 ␮m2) are present in these
strains, whereas the number of small axons (0 –50 ␮m2) and
total number of axons per ventral root is larger in CSS1 and
A/J. Also, as there is no evidence for either degeneration, for
example no myelin debris remaining after axonal degenera-
tion, nor regeneration, as the thickness of the myelin sheets
is in proportion with the diameter of the axons. This implies a
shift to smaller, less developed axons. As EphA4 is intricately
involved in the development of the neuronal circuitry that
controls locomotor behavior, the possible involvement of dif-
ferential regulation of this gene, as found for C57BL/6J and
CSS1, in these findings is fascinating. Since EphA4 is ex-
pressed on motor neurons during development (Ohta et al.,
1997), and spontaneous activity is necessary for sufficient
expression of guidance (Hanson and Landmesser, 2004), the
mechanism for motor abnormalities may be dependent on
reduced spontaneous neural activity.
When only taking C57BL/6J and CSS1 into account,
there appears to be a good correlation between the decrease
in activity levels, increase in synchronous hind limb move-
ment and the size distribution pattern of the axons within the
ventral roots. However, the additional inbred strains tested
show that the relationship between these parameters is much
more complex in nature and influenced by likely other ge-
netic, epigenetic and developmental factors.
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