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Modulation of social behavior by the agouti pigmentation gene.

Carola V, Perlas E, Zonfrillo F, Soini HA, Novotny MV, Gross CT - Front Behav Neurosci (2014)

Bottom Line: Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors.Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin.These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.

View Article: PubMed Central - PubMed

Affiliation: IRCCS Fondazione Santa Lucia Rome, Italy ; Mouse Biology Unit, European Molecular Biology Laboratory Monterotondo, Italy.

ABSTRACT
Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors. Mice and rats lacking agouti (called non-agouti) have dark fur due to a disinhibition of melanocortin signaling and pigment deposition in the hair follicle. Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin. Here we confirm that non-agouti mice show altered social behavior and uncover expression of agouti in the preputial gland, a sebaceous organ in the urinary tract that secretes molecules involved in social behavior. Non-agouti mice had enlarged preputial glands and altered levels of putative preputial pheromones and surgical removal of the gland reversed the behavioral phenotype. These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.

No MeSH data available.


Related in: MedlinePlus

Non-agouti mice are more sociable. Male non-agouti mice performed significantly more (A) attacks and showed a significantly shorter (B) latency to the first attack than male agouti littermates in the resident-intruder test (N = 10). Male non-agouti mice performed significantly more (C) social exploration and significantly less (D) environmental exploration than male agouti littermates in the social interaction test (fraction of total observations; N = 14). (E) In the olfactory approach test mice were allowed to explore two compartments during an initial exploration phase followed by a testing phase in which urine from an adult male mouse was placed into one compartment. (F) Male non-agouti mice showed a significantly greater preference for the urine-containing compartment when compared to male agouti littermates. (N = 12–13, *P < 0.05, ***P < 0.001). (G) Non-agouti mice tended to perform more scent marking than agouti mice in the urine-containing side of the apparatus used for the olfactory approach test.
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Figure 1: Non-agouti mice are more sociable. Male non-agouti mice performed significantly more (A) attacks and showed a significantly shorter (B) latency to the first attack than male agouti littermates in the resident-intruder test (N = 10). Male non-agouti mice performed significantly more (C) social exploration and significantly less (D) environmental exploration than male agouti littermates in the social interaction test (fraction of total observations; N = 14). (E) In the olfactory approach test mice were allowed to explore two compartments during an initial exploration phase followed by a testing phase in which urine from an adult male mouse was placed into one compartment. (F) Male non-agouti mice showed a significantly greater preference for the urine-containing compartment when compared to male agouti littermates. (N = 12–13, *P < 0.05, ***P < 0.001). (G) Non-agouti mice tended to perform more scent marking than agouti mice in the urine-containing side of the apparatus used for the olfactory approach test.

Mentions: Non-agouti mice showed decreased locomotion in the open field and elevated plus maze tests when compared to agouti littermates (Figure S1). We also examined aggressive-like behavior in the resident-intruder test. Non-agouti mice showed significantly increased aggressive-like behavior when compared to agouti littermates in the test, exhibiting more attacks [Figure 1A; repeated measure ANOVA, genotype effect: F(1, 18) = 5.40, P = 0.032] and a shorter latency to the first attack [Figure 1B; repeated measure ANOVA, genotype effect: F(1, 18) = 7.77; P = 0.012] toward a non-agouti intruder over three consecutive trials. To evaluate if aggressive behavior of the resident could be modulated by the genotype of the intruder a fourth trial was carried out in which each group was split and half were exposed to non-agouti and the other half to agouti intruders. No significant behavioral differences between mice exposed to agouti or non-agouti intruders were detected (Figure S2). Finally, we examined the possibility that the agouti genotype of a mouse might elicit different levels of aggression in an opponent by performing a resident-intruder test with CD1 outbred intruder mice, a strain characterized by high levels of aggressive behavior (see Supplementary Material). Under these circumstances CD1 intruders invariably attack the residents during the first encounter. However, no difference was observed in the number of attacks or latency to attack toward non-agouti and agouti residents suggesting that the indirect genetic effects of agouti on aggression are minimal (Figure S3).


Modulation of social behavior by the agouti pigmentation gene.

Carola V, Perlas E, Zonfrillo F, Soini HA, Novotny MV, Gross CT - Front Behav Neurosci (2014)

Non-agouti mice are more sociable. Male non-agouti mice performed significantly more (A) attacks and showed a significantly shorter (B) latency to the first attack than male agouti littermates in the resident-intruder test (N = 10). Male non-agouti mice performed significantly more (C) social exploration and significantly less (D) environmental exploration than male agouti littermates in the social interaction test (fraction of total observations; N = 14). (E) In the olfactory approach test mice were allowed to explore two compartments during an initial exploration phase followed by a testing phase in which urine from an adult male mouse was placed into one compartment. (F) Male non-agouti mice showed a significantly greater preference for the urine-containing compartment when compared to male agouti littermates. (N = 12–13, *P < 0.05, ***P < 0.001). (G) Non-agouti mice tended to perform more scent marking than agouti mice in the urine-containing side of the apparatus used for the olfactory approach test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4117936&req=5

Figure 1: Non-agouti mice are more sociable. Male non-agouti mice performed significantly more (A) attacks and showed a significantly shorter (B) latency to the first attack than male agouti littermates in the resident-intruder test (N = 10). Male non-agouti mice performed significantly more (C) social exploration and significantly less (D) environmental exploration than male agouti littermates in the social interaction test (fraction of total observations; N = 14). (E) In the olfactory approach test mice were allowed to explore two compartments during an initial exploration phase followed by a testing phase in which urine from an adult male mouse was placed into one compartment. (F) Male non-agouti mice showed a significantly greater preference for the urine-containing compartment when compared to male agouti littermates. (N = 12–13, *P < 0.05, ***P < 0.001). (G) Non-agouti mice tended to perform more scent marking than agouti mice in the urine-containing side of the apparatus used for the olfactory approach test.
Mentions: Non-agouti mice showed decreased locomotion in the open field and elevated plus maze tests when compared to agouti littermates (Figure S1). We also examined aggressive-like behavior in the resident-intruder test. Non-agouti mice showed significantly increased aggressive-like behavior when compared to agouti littermates in the test, exhibiting more attacks [Figure 1A; repeated measure ANOVA, genotype effect: F(1, 18) = 5.40, P = 0.032] and a shorter latency to the first attack [Figure 1B; repeated measure ANOVA, genotype effect: F(1, 18) = 7.77; P = 0.012] toward a non-agouti intruder over three consecutive trials. To evaluate if aggressive behavior of the resident could be modulated by the genotype of the intruder a fourth trial was carried out in which each group was split and half were exposed to non-agouti and the other half to agouti intruders. No significant behavioral differences between mice exposed to agouti or non-agouti intruders were detected (Figure S2). Finally, we examined the possibility that the agouti genotype of a mouse might elicit different levels of aggression in an opponent by performing a resident-intruder test with CD1 outbred intruder mice, a strain characterized by high levels of aggressive behavior (see Supplementary Material). Under these circumstances CD1 intruders invariably attack the residents during the first encounter. However, no difference was observed in the number of attacks or latency to attack toward non-agouti and agouti residents suggesting that the indirect genetic effects of agouti on aggression are minimal (Figure S3).

Bottom Line: Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors.Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin.These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.

View Article: PubMed Central - PubMed

Affiliation: IRCCS Fondazione Santa Lucia Rome, Italy ; Mouse Biology Unit, European Molecular Biology Laboratory Monterotondo, Italy.

ABSTRACT
Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors. Mice and rats lacking agouti (called non-agouti) have dark fur due to a disinhibition of melanocortin signaling and pigment deposition in the hair follicle. Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin. Here we confirm that non-agouti mice show altered social behavior and uncover expression of agouti in the preputial gland, a sebaceous organ in the urinary tract that secretes molecules involved in social behavior. Non-agouti mice had enlarged preputial glands and altered levels of putative preputial pheromones and surgical removal of the gland reversed the behavioral phenotype. These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.

No MeSH data available.


Related in: MedlinePlus