Loss of Sex Discrimination and Male-Male Aggression in Mice Deficient for TRP2

Stowers, Lisa; Holy, Timothy E.; Meister, Markus; Dulac, Catherine; Koentges, Georgy

doi:10.1126/science.1069259

Cited by 772 publications

(767 citation statements)

References 45 publications

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“…castrated males swabbed with urine of intact males (Stowers et al, 2002), but try to mount them instead, as if they interpret these intruders as females. When lactating females are used in maternal aggression tests, nest defence is also clearly impaired in trpc2 -/-mutants (Leypold et al, 2002;Kimchi et al, 2007) even when the mutation is shifted into a line of mice selected for their robust maternal aggression (Hasen and Gammie, 2009).…”

Section: Role Of the Vomeronasal And Olfactory Epithelia On Aggressionmentioning

confidence: 99%

From sexual attraction to maternal aggression: When pheromones change their behavioural significance

Martín‐Sánchez

McLean

Beynon

et al. 2015

Hormones and Behavior

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From sexual attraction to maternal aggression: When pheromones change their behavioural significance, Hormones and Behavior (2014), doi: 10.1016/j.yhbeh.2014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 AbstractThis paper reviews the role of chemosignals in the socio-sexual interactions of female mice, and reports two experiments testing the role of pup-derived chemosignals and the male sexual pheromone darcin in inducing and promoting maternal aggression. Female mice are attracted to urine-borne male pheromones. Volatile and non-volatile urine fractions have been proposed to contain olfactory and vomeronasal pheromones. In particular, the male-specific major urinary protein (MUP) MUP20, darcin, has been shown to be rewarding and attractive to females. Non-urinary male chemosignals, such as the lacrimal protein ESP1, promote lordosis in female mice, but its attractive properties are still to be tested. There is evidence indicating that ESP1 and MUPs are detected by vomeronasal type 2 receptors (V2R).When a female mouse becomes pregnant, she undergoes dramatic changes in her physiology and behaviour. She builds a nest for her pups and takes care of them. Dams also defend the nest against conspecific intruders, attacking especially gonadally intact males. Maternal behaviour is dependent on a functional olfactory system, thus suggesting a role of chemosignals in the development of maternal behaviour. Our first experiment demonstrates, however, that pup chemosignals are not sufficient to induce maternal aggression in virgin females. In addition, it is known that vomeronasal stimuli are needed for maternal aggression.Since MUPs (and other molecules) are able to promote intermale aggression, in our second experiment we test if the attractive MUP darcin also promotes attacks on castrated male intruders by lactating dams. Our findings demonstrate that the same chemosignal, darcin, promotes attraction or aggression according to female reproductive state.

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Section: Role Of the Vomeronasal And Olfactory Epithelia On Aggressionmentioning

confidence: 99%

From sexual attraction to maternal aggression: When pheromones change their behavioural significance

Martín‐Sánchez

McLean

Beynon

et al. 2015

Hormones and Behavior

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“…Cnga2 -/-mutant males do not initiate aggression with other males, but also show no social or sexual interest in females whatsoever and fail to show any mounting behaviour in tests [63]. This contrasts with the effects of the vomeronasal-specific Trpc2 -/-knockout, which disrupts male-male aggression but does not abolish copulation, but instead results in indiscriminate mounting of both males and females [80]. These gene knockouts affecting the two olfactory systems suggest that both are required for proper induction of pheromonal behaviours such as intermale aggression and mating and that the MOE may detect volatile female odours, arousing interest and stimulating active investigation and subsequent pumping of semiochemicals into the VNO lumen.…”

Section: The Main Olfactory System and Pheromonesmentioning

confidence: 82%

“…Gene knockout of the VNO-specific Trpc2 ion channel blocks signalling in all V1R neurons, and studies of mice carrying such a knockout have shown that pheromone-mediated behaviours such as male-male aggression are abolished by the knockout [80]. The signal transduction mechanism in V2R-expressing neurons appears to be different and does not involve the Trpc2 channel, as Trpc2-knockout mice remain sensitive to MHC-class 1 peptides and exhibit the pregnancy block behaviour which these semiochemicals trigger and which are mediated through V2R-expressing vomeronasal sensory neurons in the basal VNO [46].…”

Section: The Vomeronasal System In Mammalsmentioning

confidence: 99%

The evolution of pheromonal communication

Swaney

Keverne

2009

Behavioural Brain Research

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Small-brained rodents have been the principle focus for pheromonal research and have provided comprehensive insights into the chemosensory mechanisms that underpin pheromonal communication and the hugely important roles that pheromones play in behavioural regulation. However, pheromonal communication does not start or end with the mouse and the rat, and work in amphibians reveals much about the likely evolutionary origins of the chemosensory systems that mediate pheromonal effects. The dual olfactory organs (the main olfactory epithelium and the vomeronasal organ), their receptors and their separate projection pathways appear to have ancient evolutionary origins, appearing in the aquatic ancestors of all tetrapods during the Devonian period and so pre-dating the transition to land. While the vomeronasal organ has long been considered an exclusively pheromonal organ, accumulating evidence indicates that it is not the sole channel for the transduction of pheromonal information and that both olfactory systems have been co-opted for the detection of different pheromone signals over the course of evolution. This has also led to great diversity in the vomeronasal and olfactory receptor families, with enormous levels of gene diversity and inactivation of genes in different species. Finally, the evolution of trichromacy as well as huge increases in social complexity have minimised the role of pheromones in the lives of primates, leading to the total inactivation of the vomeronasal system in catarrhine primates while the brain increased in size and behaviour became emancipated from hormonal regulation.

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“…This importantly suggests that the molecular capacities of VNO neurons may have closely evolved with genetic mechanisms regulating the production of particular pheromones to which these neurons are dedicated. Recently, it has been shown that genetic ablation of a member of the TRP family of ion channels, TRP2, a putative transducer of VNO neuron signals, results in loss of the ability of male mice to discriminate between the sexes (Stowers et al, 2002). TRP2(Ϫ/Ϫ) males mount both males and females with equal frequency, and do not exhibit the typical aggressive behavior to intruder males.…”

Section: Genetic Systems Required For Detection Attraction and Discmentioning

confidence: 99%

Genetic basis of male sexual behavior

Emmons

Lipton

2002

J. Neurobiol.

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Male sexual behavior is increasingly the focus of genetic study in a variety of animals. Genetic analysis in the soil roundworm Caenorhabditis elegans and the fruit fly Drosophila melanogaster has lead to identification of genes and circuits that govern behaviors ranging from motivation and mate-searching to courtship and copulation. Some worm and fly genes have counterparts with related functions in higher animals and many more such correspondences can be expected. Analysis of mutations in mammals can potentially leadto insights into such issues as monogamous versus promiscuous sexual behavior and sexual orientation. Genetic analysis of sexual behavior has implications for understanding how the nervous system generates and controls a complex behavior. It can also help us to gain an appreciation of how behavior is encoded by genes and their regulatory sequences.

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Loss of Sex Discrimination and Male-Male Aggression in Mice Deficient for TRP2

Cited by 772 publications

References 45 publications

From sexual attraction to maternal aggression: When pheromones change their behavioural significance

From sexual attraction to maternal aggression: When pheromones change their behavioural significance

The evolution of pheromonal communication

Genetic basis of male sexual behavior

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