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1I.P.
Pavlov Institute of Physiology, Russian Academy of Sciences,
2Institute of Experimental Medicine, Russian Academy of Medical Sciences,
3Institute of Cytology, Russian Academy of Sciences
E-mail: ellena_fedorova@mail.ru
Aggressive behaviour represents universal type of social Fig 1. Testosterone influence on β-glucuronidase Table 4. Combinatorial genotype-dependent Our data on genotype- and sex-specific ratios of principal
communication system in Animal Kingdom. Aggression activity in voided urine, kidneys, salivary and MUP profiles during male mice ontogenesis MUP fractions (A, C, D, E) in CBA/LacY and C57BL/6JY
takes place between at least two animals after an intensive mice may provide new insights into mechanisms of genetic
exchange of information via several sensory modalities:
preputial glands from male mice of Genotype Age, Fractions Consequential Ratio of principal and epigenetic regulation of Mup gene cluster, which result
visual, acoustic, tactile, and chemosensory. Thus, genetic different genotypes weeks fractions’ fractions
in expression of specific bouquets of MUPs. We propose that
A B C D E F G H order
analysis of aggression is rather problematic due to complex various volatile pheromonally active ligands (e.g. SBT,
Kidneys CBA/LacY
Urine
and highly dynamic interactions between animals. In mice, 30000 C57BL/6JY 250
3 + − + + − + + + GCAHFD 0.45:0.40:0.15 HMH, DHB) represent «letters» of the chemical «language
like in many other mammals, the leading sensory modality is 25000 200 of communication» in Mus musculus L. and that,
20000
4 + + + + − + + + CADGBHF 0.60:0.25:0.15
olfaction, and much of the information is conveyed by highly 150
correspondingly, specific combinations of MUPs efficiently
F.U.
F.U.
15000
C57BL/6JY
organize these «letters» into readable «words» that encode
100
specific ligands, pheromones, which have the ability to 10000
50 8 + + + + − + + + CADBGFH 0.55:0.25:0.20
5000
initiate innate (genetically programmed) behavioural 0 0 sex, physiological state, age, and genotype differences
responses from receiver (Novikov, 1993). Sham-operated Castrated Castrated+TP Sham-operated Castrated Castrated+TP
12 + + + + − + + + CADBGFH 0.55:0.25:0.20 (Novikov et al., 2009).
The model of pheromonally mediated aggression in Mus Preputial glands Salivary glands Together with the data showing that vomeronasal neurons
musculus L. was introduced in social behaviour analysis 35
1500 10000
3 + − − + + − + + EADGH 0.40:0:30:0:30 can be directly activated by MUPs (Chamero et al., 2007),
1200 8000
years ago (Kessler et al., 1975). However, until recently 900 6000 and that expression of pheromone receptors V2Rs is sex
+ + + + + − + + DCEABGH 0.50:0.25:0.20:0.05
F.U.
F.U.
4
genetical basis of differences in physiological activity of 600 4000
CBA/LacY
specific (He et al., 2008, 2010) and combinatorial (Silvotti et
mouse androgen-dependent pheromones such as 2-sec-butyl- 300 2000
8 + + + + + − + + DECABGH 0.45:0.35:0.15:0.05 al., 2007), our results provide valuable insights into fine
0
4,5-dihydrothiazole (SBT), 6-hydroxy-6-methyl-3-heptanone 0
Sham-operated Castrated+TP Sham-operated Castrated Castrated+TP
molecular mechanisms of olfactory coding of intermale
(HMH), and 2,3-dehydro-exo-brevicomin (DHB) (Novotny 12 + + + + + − + + DECABGH 0.60:0.20:0.10:0.10 aggression in Mus musculus L. based on specific subsets
et al., 1999; Perez-Miller et al., 2010) was poorly (modules) of MUPs combinations and their interplay with
understood. Quantitative evaluation of 8 protein fractions A-H with regard to complementary sets of V2Rs.
In 2007 it was reported that the main fraction of mouse age and genotype revealed significant interstrain differences in We suggest that androgen- and genotype-dependent activity
urinary proteins with M.m.18-20 kDa, named «major urinary Fig 2. β-Glucuronidase activity in kidneys and MUPs expression patterns in male mice during postnatal
of kidney metallopeptidase meprin (EC 3.4.24.18), which
voided urine from male mice of development. According to their relative values at various
proteins» (MUPs), by itself and without pheromonal ligands probably participates in degradation of MUPs (Beynon et al.,
ontogenetic stages, we divided these MUP fractions into two
(SBT, HMH, DHB) could efficiently promote aggressive different genotypes subsets that probably reflect their different functional significance. 1996), is tightly linked with pheromonal activity of several
reactions from the recipient (Chamero et al., 2007). It means The first subset, which could be characterized as «ontogenetically oligopeptides (Tsujikawa, Kashiwayanagi, 1999; Kimoto et
that MUPs are a powerful tool for genetical dissection of Kidneys Urine stable», consists of fractions A, C, D, and E; the second subset al., 2005, 2007). This peptidase is encoded by Mep1a gene
10000 500
social behaviour (Novikov, 2007, 2008). 8000 400
consists of fractions B, F, G, and H, which are significantly mapped to chromosome 17 near the main histocompatibility
In 2003 we put forward an idea that genes Mup, Gus and 6000 300 influenced by the age factor (Chemical Senses, in preparation). locus H-2. Taking into account that H-2 complex also
F.U.
F.U.
2000
200
100
participates in olfactory-mediated social recognition in mice
(Novikov, 2003). Gus gene is located on chromosome 5 and 0 0 (Boehm, 2006, 2009; Brennan, Kendrick, 2006; Rodriguez,
encodes β-glucuronidase (GUS, EC 3.2.1.31), which
CBA/LacY CBAB6F1 B6CBAF1 C57BL/6JY CBA/LacY CBAB6F1 B6CBAF1 C57BL/6JY Table 5. Combinatorial genotype-dependent Boehm, 2009; Tirindelli et al., 2009; Kwak et al., 2010), we
Genotype Genotype
activates latent aggression-promoting cues in mouse urine MUP codes for gender and physiological propose for the first time that Gus, Mup, Mep1a, and H2
(Ingersoll et al., 1982). Mep1a is mapped to chromosome 17 state in mice genes represent an «aggressive behaviour gene net» in Mus
and encodes meprin (EC 3.4.24.18), a metallopeptidase that musculus L. (Figure 4).
Genotype Physiological Fraction Consequential Ratio of principal
probably participates in degradation of MUPs (Beynon et al., state fractions’ fractions
1996). Mup multigene locus is located on chromosome 4. In Table 1. Correlation between plasma A B C D E F G H order Fig 4. Proposed «aggressive behaviour gene net»
the current study, we examined the idea of the «gene testosterone level and β-glucuronidase activity in females + + + − − + + + CABFGH 0.80:0.20
in Mus musculus L.
network» in details. Quantitative analysis of plasma kidneys and voided urine from male mice of
testosterone level, MUPs content and GUS activity in voided different genotypes castrates + + + − − + + + CABFGH 0.50:0.50
urine, kidney, preputial and salivary glands in male mice of C57BL/6JY
different genotypes revealed a strong correlation between castrated+T + + + + − + + + CADBFGH 0.40:0.35:0.25
Kidneys Urine
plasma testosterone level, GUS activity, and differential Genotype males + + + + − + + + CADBFGH 0.40:0.30:0.30
pattern of Mup gene expression. F.U. F.U./mg tissue F.U.
females + − − + + − + + EADHG 0.50:0.35:0.15
CBA/LacY +0.670* +0.702* +0.851**