Copyright 0 1994 by the Genetics Society of America
Co-Segregation of Intermale Aggression With the Pseudoautosomal
Region of the Y Chromosome in Mice
Pierre L. Roubertoux, Michele Carlier, Herve Degrelle, Marie-Claude Haas-Dupertuis,
John Phillips and Rene Moutier
U.R.A. 1294 C. N. R.S. Ginitique, Neuroginitique,
Comportement, Uniuersiti Paris-V ReniDescartes,
75270 Paras, Cedex 06,France
Manuscript received March 23, 1993
Accepted for publication September 1 1, 1993
ABSTRACT
The sexual dimorphism of aggression has led atosearch for its Y chromosomal correlates. We have
previously confirmed that initiation of attack behavior against a conspecific male is Y-dependent in
two strains of laboratory mice (NZB and CBA/H).We provide evidence that the non-pseudoautosomal
region of the Y is not involved and that only the pseudoautosomal region of the Y is correlated with
initiation of attack behavior. The autosomal correlates also contribute to this behavior in an additive
or interactive manner with the pseudoautosomal correlates.
parsimonious hypothesis to reconcile both arguments:
HE association of differences in agonistic behava non-pseudoautosomal region of the Y chromosome
ior, defined as the initiation of attack behavior
(Y”’””) is transmitted from father to son, whereas all
against a conspecific male, with the variants of the Y
or part of the other region of the Y chromosome
chromosome in mice is the subject of a long-standing
et al. 1990; CARLIER, ROUBERTOUX recombines with the X chromosome and is thus
debate (CARLIER
termed “pseudoautosomal region” (Y‘””). This sharand PASTORET
199 1; MAXSON1992a,b). On the one
ing
of the YPARby both males and females is compatible
hand, three independentresearch teams using inbred
with
a commonY correlate for attackbehavior in both
strains of laboratory mice have implicated the Y chrosexes,
and the so-called “autosomal” co-acting or inmosome in initiation of attack behavior against conteracting
genes would, in fact, be “pseudoautosomal,”
specific males, either from the comparison of strains
i.e.,
located
on the YPARas previously suggested (CARcongenic for the Y chromosome (MAXSON,
GINSBURG
LIER
et
al.
1990). Malemice fromstrain NZB/BI1979; STEWART,MANNING and
and TRATTNER
NJGnc
(abbreviated
N hereafter)display more intense
BATTY 1980) or fromresults of mendelian crosses
and
frequent
spontaneous
offensive behavior against
(CARLIER,
ROUBERTOUX
and PASTORET
199 1). Moreconspecific
males
than
CBA/HGnc
mice (abbreviated
over the Y chromosome has been implicated in differH)
(CARLIER
and
ROUBERTOUX
1986).
The frequency
ences between lines selected for short vs. long attack
of
males
initiating
attack
behavior
is
higher
in N than
latency from a populationof feral mice (Mus musculus
in
H
for
dyadic
encounters
with
a
standard
opponent.
1984;VANOORTdomesticus; VAN OORTMERSSEN
Moreover,
when
the
maternal
environment
is kept
MERSSEN, BENUSand SLUYTER 1992).On the other
constant,
this
difference
is
not
modified,
showing
that
hand, a correlated response for female aggression in
the
observed
strain
difference
has
genetic
and/or
cylines differentially selected only for male aggression
toplasmic
correlates.
We
have
previously
demonhas been reported (HOODand CAIRNS1988) suggeststrated that atleast one locus on the Y chromosome is
ing that this behavior may not be transmitted by a
associated
with attack behavior in these populations
locus linked to the Y chromosome. It is worth noting
(CARLIER, ROUBERTOUX
and PASTORET
1991), but it
that in the studies using inbred strains, the Y effect
was not known whether this locus is located on the
always acts concomitantly with the autosomal backYNPAR
or on the YPAR.In the present study we describe
and TRATTNER
1979;
ground (MAXSON,GINSBURG
a co-segregation of the YPARwith the initiation of
et al. 1990).
CARLIER
attack behavior.
The opposing conclusions drawn between the results of HOODand CAIRNSand the otherteams could
be due to differences in behavioral testing, rearing
MATERIALS AND METHODS
conditions, or in differences in the genetic informaMice: Identified breeders from two highly inbred strains
tion borne either on theautosomes or on the Y chroof mice were used: H and N. They were supplied by the
mosome. Obligatory crossing over between the X and
CSEAL (CNRS, Orlians la Source, France) at 127 and 1 14
the Y chromosomes (SIMLERet al. 1985; ELLISand
brother X sister generations of mating, respectively, and
GOODFELLOW
1989) at the male meiosis leads toa
had been maintained using the same mating system, in our
T
Genetics 135 225-230 (January, 1994)
226
P. L. Roubertoux et al.
laboratory, for a further 8 generations at the beginning of
the experiment.
Rearing conditions:The following conditions have been
kept constant over the years: temperature 23.5" & 0.5";
photoperiod, 12:12 withlights on at 8:30 AM; food (IM
UAR) and tap water ad libitum; dust-free sawdust bedding;
weaning 30 & 1 days after birth. Each pregnant female was
isolated from the mating cages. The litters having fewer
than four pups were discarded and the others culled to six
pups. At weaning, each male was housed with one female
(generally a littermate) in an opaque cage (42 X 27 X 17
cm) until testing (66 If: 4 days after birth).
Behavioral testing: The conditions of observation and
measurement (described by CARLIERand ROUBERTOUX
1986) were maintained unchanged for all groups over the
years. Briefly, the test was performed in a transparent cage
(42 X 26 X 18 cm) with a transparent lid. The floor of the
cage was covered with sawdust from several cages housing
males of the tested groups. This procedure accelerates the
appearance of the first attack (CARLIER
and ROUBERTOUX
1986). Several observations were carried out on a given day
and the groups were matched for order of observation. Each
test was a dyadic encounter with an A/JOrl (A) male as the
opponent. This strain had been chosen for its low scores of
aggression and, in fact, the A males rarely initiated attack.
The males tested in such a situation were discarded. The A
opponent came from a group male cage. The behavioral
records started when the tested male sniffedthe Aopponent
for the first time, and the test lasted 6 min in cases where
no attack occurred. Several variables were measured but
only the frequency of attacking males will be considered
here.
Crosses: Only crosses informative for the demonstration
of a co-segregation betweenthe YPARand initiation of attack
behavior are reported here.
First, congenic strains for YNPARwere developed in 1983
in
by CARLIER.
The H-YNPAR was
substituted by the N-YNPAR
the H strain to obtain its congenic H.N-YNPAR
for this region
of the Y chromosome and secondly by substituting the HYNPAR in the place of the N-YNPARin the N strain to obtain
its congenic N.H-YNPAR.
The congenic N.H-YNpAR
was developed with N as recipient strain andH as donor, the N
females being sired by NHF, males (in each cross the mother's genotype will be given first, separated by x from the
father's genotype; within each genotype the first letter+)
indicate the strain of the mother) and the backcross males
subsequently sired again with N. The symmetrical design
was used to obtain the second congenic H.N-YNPAR.
The
N.H-YNpAR
and the H.N-YNPAR
reached 29 and 30 backcross
generations, respectively, and were observed between the
2nd and 21st repeated backcross. At every generation it is
assumed that the congenic progeny lose 50% of the alleles
from the congenic donor. Thus more than 99.99% of the
allelic forms of the parental recipient strain, located
throughout the genotype, including the YPAR, are expected
in the congenic, at the 21st backcross. The isogenicity of
the genetic background was directly confirmed by skin graft
acceptance and by the similarity of mandible shape. First,
tail skinreciprocal graftings were performed in females from
H and H.N-YNPAR
on one hand, and from N and N.H-YNPAR
on the other, at the 9th
backcross generation. One rejection
out of 11 was observed in the first group and none in the
second, 347 days afterthe graft. Second, 11 mandible
measurements were performed on the same four groups.
There is a high similarity for pairwise squared distances for
a pair of congenic strains under thehypothesis of isogenicity,
since BAILEY(1985) estimated the number of genes responsible for morphological changes on murine mandible to be
over 100. No significant difference was found within the
same sex between H vs. H.N-YNPAR
and between N vs. N.HYNpAR (MOUTIERand CARLIER
1991).
Second, the parental H and N females were sired with
the parental and congenic males, thus providing two sets of
recirocal Fls: HNF,,NHF, on one hand and HN.HYNp RF1,NH.N-YNPARFI
on the other. Theselast two groups
were constituted afterthe8th
generation ofbackcross.
Results on HNF, and NHF, have already been published
ROUBERTOUX
(CARLIER
and ROUBERTOUX
1986; CARLIER,
and PASTORET
1991). New groups have since been studied
and because these gave very similar results, the data of all
the males from the same F, were grouped.
Third, two sets of backcrosses were developed with H
and N parental males on reciprocal HNF, and NHF, mothers: HN X H, HN X N, NH X H, and NH X N.
Fourth, reciprocal backcrosses on FI mothers whose ovaries had been removed and replaced in situ by ovaries from
parental strains were obtained. As NHF, females are histocompatible with H andN tissues, their ovaries wereremoved
and replaced by ovaries from N or H females according to
a technique described previously (ROUBERTOUX
and CARLIER 1988; ROUBERTOUX,
NOSTEN-BERTRAND
and CARLIER
1990; CARLIER,NOSTEN-BERTRAND
and MICHARD1992).
The females were labeled NoFl (for those providing N ova)
or HoFl (for those providing H ova). Two controls were
performed: first, to test for a transplantation effect per se,
intrastrain ovary transplantations wereused: males born
from NoNfemales (N femaleswhoseovaries
had been
removed and replaced in situ by ovaries from the N strain)
were compared to those with identical genotype born from
ungrafted N females, a symmetrical procedure being employed for HoH and H females. No effect due to grafting
has been shown for initiation of attack behavior (ROUBERTOUX and CARLIER
1988). Second, controls for thegenotype
of the pups were required because part of the ovary of the
host female canremain after ovarectomy. Four independent
genetic markers (coat color and threeelectrophoretic markers) were used to detect discrepancies between the expected
and observed genotypes. Individuals were first observed in
the behavioral test, theywere then typedemploying the
four genetic polymorphic markers. Only those for which
the observed genotype fitted the expected were considered
for the subsequent statistical analysis. One subject was discarded for this reason in the NoFl X HN backcross (leading
to an observed error rate of 1/65).
Genetic polymorphism for the YPAR;measurement of
liver steroid sulfatase(STS)activity: The hypothesis of cosegregation of the YpAR and initiation of offense behavior,
can be tested using known differences between N-YPARand
H-YPAR.
The liver STS (EC 3.1.6.2) activity is controlled by
the Sts locus (mapped on the YPAR;
KEITCES et al. 1985) and
was therefore used as a marker. The technique of measurement of the initial production rate of ['Hlestrone from ['HI
estrone sulfate (expressed as picomoles of ['Hlestrone produced per min and permg protein; PROSTand ADFSSI 1983)
was modified from BURSTEINand DORFMAN(1 963). Briefly,
(1) the substrate concentration must not be rate-limiting
since the catalysis is inhibited by an excessof substrate.
Thus, to obtain the V,,, and K , from the Lineweaver-Burk
reciprocal plot, we performed three substrate concentrations and a zero time to detect possible free steroid (each in
duplicate). (2) Chromatographic purification of the radioactive substrate was needed since it can be partially hydrolyzed and/or radiolyzed. (3) The reaction was stopped with
NanCOs (and not NaOH) to prevent ionization of free
estrone, which was extracted using petroleum benzine.
The liver STS activity was measured in males from the
parental and their congenic strains, and alsoin NH.NyNPARFI and HN.H-YNpARFI
males.
R
Intermale Aggression
Statistics and experimental design: The differences between proportions of attacking males were tested here with
a logit model analysis using the SAS CATMOD procedure.
All the main effects and interactions are included in this
model and tested according to ananalysis ofvariance design
as indicated in the SAS/STAT Guidefor Personal Computers
(1 987).
The contribution of the YNPAR to initiation of attack
behavior was tested by comparing males from each parental
and its congenic strain. The behavioral observations were
not performed at each generation of the congenics after
backcross 4. The statistical analysis was performed by pooling the generations 2-6, 7-1 3 and 14-21 within each congenic. A group of each corresponding parental strain was
observed each year allowing a comparison between the
congenic andtheir parental strains. The proportions of
attacking males were thus compared with a 3 X 2 X 2 desi n;
three groups of generations and parental strains, two YN A R
(H and N) and two backgrounds (H and N).
The two sets ofreciprocal Fls from parental females sired
with parental and congenic males constitute a segregating
population for theseparation of the possible contribution of
YN AR and YPAR. The HNFl and HN.H-YNPARFI
share the
same YpAR from N and have different non-pseudoautosomal
re ions. Similarly, NHFl and NH.N-YNPARF1
share the same
YpB from H but have different non-pseudoautosomal regions. A logit model analysisof the attack proportions
following a 2 x 2 design was thus performed to test for the
effect of each part of the Y (pseudoautosomal and nonpseudoautosomal). However, other candidate factors (the
maternal environment, differential genomic imprinting, mitochondrial DNA and the X chromosome) also covary with
yNPAR and YPAR,in these crosses, and thus might be responsible for an apparent co-segregation of one part of the Y
with initiation of attack behavior in these reciprocal Fls. It
was thus necessary to eliminate the possible effects of these
factors.
The contribution of differences in maternal environment
can be eliminated if the co-segregation of one part of the Y
and initiation of attack behavior stillpersistswhenthis
environment is kept constant. Moreover, possible differential genomic imprinting (for example, the X from H inhibiting the expression of N-YNPARin the subjects having received H-YPAR)
is not compatible with a co-segregation which
is alwaysfound in the backcrosses, regardless of whether the
genotypic contribution of the mother is H or N. The effect
of these potential factors were tested employing reciprocal
backcrosses on F1 mothers bearing in situ grafted ovaries
from N and H.
The mitochondrial DNA (mtDNA) is almost entirely maternally transmitted (GYLLENSTEIN
et ul. 1991) and H and
N mothers have mtDNA from different origins, domesticus
and brwirostris, respective1 (YONEKAWA
et al. 1982). Consequently, the HN.H-YNPA$,males that bear the N-YPAR
have alsoinherited the mtDNA from H, whereas the NH.NYNPARFl,
bearing the H-yPAR,have received the mtDNA from
N. Backcrosses from the reciprocal F1 females provide the
opportunity to test for an implication of mtDNA on initiation of attack behavior. Offspring of the first set of backcrosses with reciprocal F1 females HN X H and HN X N
compared to those of the second NH X H and NH X N,
have, in probability, the same number of autosomal or
linked allelic forms from N and H, an identical Y chromosome and are exposed to identical maternal effects. They
only differ by the origin, H us. N, of mtDNA and were used,
here, to test for its implication in initiation ofattack behavior.
us. the NHFl and NH.NThe HNFI and HN.H-YNPARFI
YNPARF
1 also differ by the X chromosome from H us. N. The
9
x-
227
sources of variation between the backcrosses from F1 females
with parental males and the backcrosses from FI females
bearing N or H ovaries with HNF, and NHFl males are
presented in Table 1.
In each pair, 1 us. 1’ or 2 us. 2’, the two backcrossesshare
identical autosomal information and maternal environment
(uterine and postnatal). They differ by the origin of the
yNPAR and a parental N or H or a recombinant X chromosome. A possible involvement of this chromosome in the
initiation of attack behavior could be deduced for thewithinpair com arisons pending the demonstration of an absence
of the YZAR effect, deduced from the congenic strains.
The liver STS activity was compared by analysis of variance.
RESULTS
The parental and their congenic strains:
The percentages of attacking males are presented in Figure 1
for the three groups of congenic and parental strains.
The three groups of pooled backcrosses and their
corresponding parental groups differ (x& = 8.85, P
= 0.01). Inspection of Figure 1 shows that males tend
to attack less in the groups of the more recent generdeations.However,theinteractionsbetweenthis
crease andthe background on one hand and
the YNPAR
on the other
are not significant (x& = 0.36, P = 0.83,
and x& = 0.98, P = 0.61). The H and N background
effect is significant (x(?)= 52,35, P < 0.0001): the
percentage of attacking males is higher in N than in
a n d ROUBH , as we have previously shown (CARLIER
ERTOUX 1986). The YNPAR effect is not significant
(x(?,= 0.14, P = 0.70) nor is the interaction between
the H and the N background and the YNPAR (x(:, =
0.30, P = 0.58).
The reciprocal Fls: The percentage of attacking
of reciprocal Flsare presented in
males in each group
Figure 2. The effect ofthe non-pseudoautosomal part
of the Y and the interaction between the two parts
of
t h e Y a r e n o significiant
t
(x$,= 0.000). However, the
effect of the pseudoautosomal region plus maternal
effects, including the mtDNA and theX contribution
is significant (x(?)
= 10.43, P = 0.001): the two groups
having the pseudoautosomal part of the Y from the
N strain (HNF1 and HN.H-YNPARFl)
attack more frequently, suggesting that if the difference between the
reciprocalFls is borne on the Y chromosome it is
independant of the genetic information borne on the
p P A R
The backcrosses with reciprocal F1 females: The
sample sizes and the percentages of males that initiated
attack behavior in the offspring
of the backcrosses
were: H N X H ( n = 21; 38.09%), HN X N (n = 20;
SO%), NH X H ( n = 24; 29.17%) and NH X N (n =
26; 69.23%). Only the origin of the father reached
the level of significance (x(?)= 14.80; P < 0.0002).
T h e males born from HNFI or NHFl mothers did
not differ (x(?)= 1.06; P = 0.30). Consequently, as n o
effect of the mother was detected, the present data
suggest that attack behavior differences are independant of mtDNA origin in these
strains.
228
P. L. R o u b e r t o u x et al.
TABLE 1
Sources of variation between reciprocal backcrosses on F1mothers bearing H and N ovaries. NoFI:FIfemales bearing N ovaries;
HoFI:FIfemales bearing H ovaries; NPAR, non-pseudoautosomalregion; PAR, pseudoautosomal region
PAR
Backcross generations
Maternal
environment
mtDNA
FI
FI
FI
FI
N
N
H
H
NOFIX N H ( 1 )
NHFl X N (1 ')
HoFl X H N (2)
HNF1 X H (2')
EN.H-Y
;I
x, 51) 128
Autosomes
314 N
314 N
114 N
114 N
oo 1; 11, 02
2 to6
7 to 13
14to21
Generations of backcrosses
FIGURE1 .-Percentage (+sE) of attacking males for thecongenic
and parental strains at three stages of backcrosses. N , number of
subjects
[-n.
?
z:
5:
38
N114 H
114 H
H314 H
314 H
H
N
N
H
FI
H
FI
On Y
XNPAR
FI
N
FI
H
N
FI
FI
1z1 H.N-Y NPAR
NPAR
-li I O I n 51)
c
On X
yNPAR
z
151
FIGURE2.-Percentage (+sE) of attacking males for four groups
of reciprocal Fls between parental strains H and N and between
parental and congenic strains H.N-ppARand N.H-ppAR.Number
of subjects are indicated under the x axis.
Reciprocal backcrosses from HNFl, NHFI, NoFl
and HoFl females: There was no effect of the YNPAR
on the phenotype under study and thus the equations
1 , 1 ', 2, 2' could be used to test for the effect of the
parental (H or N) us. X chromosome recombining H
and N information. The comparisons for proportions
of attacking males differ neitherbetween ( 1 ) offspring
of NoFl X NH (n = 15; 93.33%)and ( 1 ') offspring of
NHFl X N (n = 26; 69.23%)(x:(1,2 = 1.97; P = 0. lo),
nor between (2) offspring of HoFl X HN (n = 22;
13
I
FIGURES."Percentage (+SE) of attacking males in offspring of
reciprocal backcrosses usingFI mothers bearing H or N ovaries and
FI males. Number of subjects are indicated under the x axis (from
CARLIER, ROUBERTOUX
and PASTORET199 1).
36.36%) and (2') offspring of HNFl X H (n = 21;
38.10%)(x(?,= 0.14; P = 0.9 1).
Reciprocal backcrosses on F1 mothers bearing H
or N ovaries: The four groups were: NoF, X NH (n
= 15), HoFl X NH (n = 14), NoFl X HN (n = 13)
and HoFl X HN (n = 22). Here the maternal environment effects are kept constant. Underthese conditions
(Figure 3), there is an effect of the genotype of the
mother H us. N (x(?)= 5.03; P < 0.03): i.e., the male
progeny attack lesswhen born from H rather than
from N females. An effect of the genotype of the
father is also shown (x:l) = 5.94; P < 0.02). The partial
comparisons demonstratethatthe
male offspring
from NHF, fathersthat have received the H-YNPAR
and the N-YPARattack more frequently than themales
from
which have received the N-YNPARand theH-YPAR
HNFl fathers, whatever the genotype or the maternal
(CARLIER,
environmentprovided
by themother
ROUBERTOUXand PASTORET199 1).
The liver STS activity :The activity ofthis enzyme
(Table 2) had a significantly lower value in the H and
H.N-YNPAR which
share the same H-YPAR
compared to
share the same N-YPAR,
the N and N.H-YNPAR which
the other sources of variation, including the interaction between the YNPARand the autosomes, were not
significant. This result indicates that two different
allelic forms of the Sts gene correspondingto different
levels of enzymatic activity are borne on the N-YPAR
Intermale Aggression
229
TABLE 2
Steroid sulfatase activity (pmol/min/mg protein)
in parental and congenic strains and
one of their reciprocal hybrids(n, number of
subjects; see text for other abbreviations)
Genotypes
9
n
R f SE
N
5
167.2 f 29.1
141.4
(4
N.H-PpAR
* 14.5
77.8
(a)
H.N-PpAR
H
8 5
f 16.7
56.8
(b)
8
f 5.6
(b)
H N .NHH- Y
. NN- ~Y~N~~F~, ~ F ,
6
32.0 f65.43
9.3
(4
f 5.1
(4
The strains with the same letter in the last row did not differ. The difference between (a) and (b) is significant: F(2,26)
= 23.48 (P< 0.001),
as is the difference between (c) and (d): t(9) = 2.97 (P< 0.05).
and H-YPAR.Moreover, the significantly lower STS
activity found in the NH.N-YNPARFI
compared to the
HN.H-YNPARF1,
suggests an under-expression of Sts
when carried on the XPAR inthese strains. The identical activities for the Y- and X-borne loci reported by
JONES et al. (1 989) are most probably limited to the
Sts silent allele employed by these authors.
DISCUSSION
The percentage of males initiating attack behavior
is higher in strain N than in H for dyadic encounters
with an A male as standard opponent as shown in
Figure 1. We know that this difference has at least
onegeneticcorrelate(CARLIER,ROUBERTOUX and
PASTORET1991). The present results indicate that
one locus is located on the YPAR.
Co-segregation of initiation of attack behavior with
YNPARwas first examined using the permutation of the
yNPAR between strains N and H (Figure 1). Independent segregation between initiation of attack behavior
and YNPARappears as soon as the first backcross and
still persists at the2 1st. This clearly demonstrates that
the locus is not on the YNPAR. On the contrary, the
absence of dissociation between the initiation of attack
behavior and the YPAR in different segregating generations, strongly suggests that the genetic correlates
for attack behavior are located on the YPAR chromosomal region.
The groups HN.H-YNPARF1,
and HNFl (sharing the
same YPAR from N and having different Y non-pseudoautosomal regions) have ahighattackbehavior,
whereas NH.N-YNPARFl
and NHFl (sharing the same
Y non-pseudoautosomal
yPAR fromHbutdifferent
regions) have a low attack behavior (Figure 2). Other
factors,presented in the experimentaldesign, also
covary with YPARbut the results presented here show
that they have no significant effect. (1) Initiation of
attack behavior is independent of the origin of
mtDNA, as shown here by the comparison of backcrosses with reciprocal F1 females. (2) For several
reasons, the X chromosome cannot contribute to the
difference in frequency of initiation of attack behavior. First, there is a poor likelihood of its involvement
since the individuals which have received the X from
H, the less attacking strain, attack more frequently
than those which have received the X from N, the
more attacking strain. Second, the association of NYPARwith a high incidence of attack behavior is always
present in the reciprocal backcrosses on F1 mothers
whether they bear H or N ovaries (and consequently
an H or an N X chromosome). Third, the inheritance
of an X chromosome either from H or N compared
to an X recombining H and N information, did not
produce any difference in the incidence of attack
behavior. (3) The covariation of the frequency of
attack behavior with YPAR still persists when the maternal environment is kept constant, in the reciprocal
backcrosses on F1 mothers bearing H or N ovaries: in
the experiment illustrated in Figure 3 only the pseudoautosomalregion was correlated with the attack
behavior in the expected direction. (4) Possible differential genomic imprinting (X from H inhibiting the
expression of N-YNPAR)in the subjects having received
H-YPAR,
is not compatible with the frequency of attack
behavior differences always found to be in the same
direction in the backcrosses, regardless of whether the
genotypic contribution of the mother is H or N.
The agreement of the data presented herewith the
hypothesis of a genetic correlate of attack behavior
located on the pseudoautosomal part of the Y chromosome is reinforced by the demonstration of an
enzymatic polymorphism for H-YPARand N-YPAR.
However, high attack behavior is associated with the
N genetic information of the pseudoautosomal region
only when it is borne on the Y chromosome and not
on the X. On the other hand, the low frequency of
attack behavior is associated with the genetic information from H, only when it is borne on the YPARand
not on the XPAR.The description of a polymorphism
for the Sts gene, previously mapped on this region,
strengthens this hypothesis. We have observed (Table
2) thattheSTS
enzymatic activity is higher when
measured in individuals bearing the N-YNPAR
and the
H-XNPAR
compared to those bearing the H-YNPAR
and
the N-XNPAR,
suggesting that the contribution to the
phenotype could vary, according to theregion (on the
X or on the Y) on which it is borne. However, the
differences in attack behavior do not seem to be the
consequence of a pleiotropic effect of allelic substitutions at the Sts locus, as suggested by the positive
correlation between attack behavior and STS enzymatic activity, in N and H strains. This correlation
230
Roubertoux P. L.
becomes negative with other strains: the C57BL/10
males that attack less than DBA/1 (SELMANOFF, MAXSON and GINSBURG
1976) have a significantly higher
STS enzymatic activity (67.9 & 15.2 vs. 41.9 & 6.7; unpublished).
The YPARalone cannot be considered responsible
for the difference in this behavior since the offspring
of the backcrosses from a mother belonging to the
more attacking strain N attack more frequently than
those of the backcrosses from an H mother (less attacking strain), when the strain of the father and the
maternalenvironment are held constant (NoFI X
HNFl > HoFl X HNFl and NoFl X NHFl > HoFl X
NHF]); see Figure 3. Thus autosomal homozygotic
alleles clearly also contribute to the difference either
in an additive or interactive manner with the YPAR.
We thank W. E. CRUSIO,B. DRESP, P.MANDELand B. MARTIN
for useful advice and J. HIRSCHand S. C. MAXSON for discussion
and suggestions during thepreparation of the manuscript. We also
thank our anonymous referees for their helpful comments. This
workwas supported by CNRS (URA 1294), DRED (Universitk
Paris V Renk Descartes), Fondation pour la Recherche Mkdicale,
Naturalia et Biologia, NATO Grant 0235/89, and Universiti de
Reims Champagne Ardenne.
L I T E R A T U R E CITED
BAILEY,
D. W., 1985 Genes that effect the shape of the murine
mandible. Congenic strain analysis.J. Hered. 7 6 107-1 14.
BURSTEIN
S., and R. I. DORFMAN,
1963 Determination ofmammalian steroid sulfatase with7-aSH 36-hydroxyandrost-5-en17-one sulfate. J. Biol. Chem. 238 1656-1660.
CARLIER, M., M. NOSTEN-BERTRAND
and C. MICHARD,
1992 Separating genetic effects from maternal environmental
effects, pp. 1 11-1 26 in Techniquesf o r the Genetic Analysisof the
Brain and Behavior: Focus on the Mouse, edited by D. GOLDOWITZ,D. WAHLSTEN
and R. WIMER.Elsevier, Amsterdam.
CARLIER,
M., AND P. L. ROUBERTOUX,
1986 Differences between
CBA/H and NZB mice on intermaleaggression. I. Comparison
between parental strains and reciprocal Fls, pp. 47-57in
Genetic Approaches to BehavioralPhenotypes, edited by J. MEDIONI and G. VAYSSE.
Privat, Toulouse.
CARLIER,
M., P. L. ROUBERTOUX
and C. PASTORET,
1991 The Y
chromosome effect on intermale aggression in mice depends
on the maternal environment. Genetics 129 231-236.
CARLIER,M., P. L. ROUBERTOUX,
M. L. KOTTLER and H. DEGRELLE,1990 Y chromosome and aggression in strains of
laboratory mice. Behav. Genet. 20: 137-156.
ELLIS,E., and P. N. GOODFELLOW,
1989 The mammalian pseudoautosomal region. Trends Genet. 5: 406-4 10.
GYLLENSTEN,
U.,D. WHARTON,
A. JOSEFSSON and A. C. WILSON,
1991 Paternal inheritance of mitochondrial DNAinmice.
Nature 352: 255-257.
HOOD,K. E., and R.B. CAIRNS,1988 A developmental-genetic
et al.
analysisof aggressivebehavior in mice.11. cross-sexinheritance.
Behav. Genet. 1 8 605-619
JONES,J., J. P. PETERS,C.RASBERRY and B. M. CATTANACH,
1989 X-inactivation of the Sts locus in mouse: anomaly of the
dosage compensation mechanism. Genet. Res. 53: 193-199.
KEITGES,
M. RIVEST,M. SINISCALCoandS. M. GARTLER,
1985 Xlinkage of steroid sulphatase in the mouse is evidence for a
functional Y-linked allele. Nature 315: 226.
MAXSON,S. C., 1992a Methodological issuesin genetic analyses
of an agonistic behavior (offense) in male mice, pp. 349-374
in Techniquesfor the Genetic Analysis of the Brain and BehavMr:
D. WAHLSTEN
Focus on the Mouse, edited byD. GQLDOWITZ,
and R. WIMER.Elsevier, Amsterdam.
MAXSON,
S. C., 1992b Potential genetic models of aggression and
violences in males, pp. 174-188 in Genetically Dejned Animals
Models of Neurobehavioral Dysfunctions, edited by P. DRISCOLL.
Birkhauser, Boston.
MAXSON,
S. C., B. GINSBURG
and A. TRATTNER,
1979 Interaction
ofY-chromosomal gene@) in the development of intermale
aggression in mice. Behav. Genet. 9 219-226.
MOUTIER,
R., and M. CARLIER,1991 Mandible shape analysisin
Y-congenic strains of mice. Lab. Anim. 2 5 303-307.
PROST,O., and G. L. ADESSI,1983 Estrone and dehydroepiandrosterone sulfatase activities in normal and pathological human endometrium biopsies. J. Clin. Endocrinol. Metab. 5 6
653-661.
ROUBERTOUX,
P. L., and M. CARLIER,
1988 Differences between
CBA/H and NZB mice on intermale aggression. I1 Maternal
effects. Behav. Genet. IS: 175-184.
ROUBERTOUX,
P. L., M. NOSTEN-BERTRAND
and M. CARLIER,
1990 Additive and interactive effects between genotype and
maternal environments, concepts and facts. Adv. Study Behav.
1 9 205-247.
SAS/STAT, 1987 Guide for Personal Computers, Version 6 Edition,
SAS Institute Inc., Cary, N.C.
B.
SELMANOFF,M. K., S. C. MAXSON and GINSBURG,
1976 Chromosomal determinants of intermale aggressive behavior in inbred mice. Behav. Genet. 6: 53-69.
SIMMLER
M. C., F. ROUYER,
G. VERGNAUD,
M.,NYSTROM-LAHTI,
K. Y. NGO, A. DE LA CHAPELLEand J. WEISSENBACH,
1985 Pseudoautosomal DNA sequences in the pairing region
ofthe human sex chromosomes. Nature 317: 692-697.
STEWART,
A. D., A. MANNINGand J. BATTY, 1980 Effects on y
chromosome variants on themale behaviour of themouse MUS
musculus. Genet. Res. 35: 261-268.
VANOORTMERSSEN,
G. A., 1984 A behavioral-genetic approach
to variation in attack latency, serum testosterone level, and
other agonistic parameters. Aggressive Behav. 1 0 177-1 78.
VAN OORTMERSSEN,
G. A,, R. F. BENUSand F. SLUYTER,
1992 Studies on wild house mice. IV. On the heredity of
testosterone and readiness to attack. Aggressivee Behav. 1s:
143-148.
YONEKAWA,
H., K. MORIWAKI,0. COTOH,N. MIYASHITA,s. MIGITA, F. BONHOMME,
J. P. HJORTH,M. L. PETRASand y. TAGASHIRA,1982 Origins of laboratory mice deduced from
restriction patterns of mitochondrial DNA. Differentiation 22:
222-226.
Communicating editor: R. E. GANSCHOW