scholarly journals Protein pheromone MUP20/Darcin is a vector and target of indirect genetic effects in mice

2018 ◽  
Author(s):  
Sven O. Bachmann ◽  
Ellen Cross ◽  
Shireene Kalbassi ◽  
Matthew Alexandar Sarraf ◽  
Stéphane J. Baudouin ◽  
...  
Keyword(s):  
Social Behavior ◽  
Mouse Model ◽  
Genetic Effects ◽  
Urinary Protein ◽  
Major Urinary Protein ◽  
Behavioral Phenotypes ◽  
Adhesion Protein ◽  
Adult Mice ◽  
Indirect Genetic Effects ◽  
Mammalian Pheromones

AbstractSocial behavior in animals is an adaptive process influenced by environmental factors and direct and indirect genetic effects. Indirect genetic effects (IGEs) include mechanisms by which individuals of particular genotypes can influence the behavioral phenotypes and genotypes (via modulated patterns of gene expression) of other individuals with different genotypes. In groups of adult mice, IGEs can be unidirectional, from one genotype to the other, or bidirectional, resulting in a homogenization of the behavioral phenotypes within the group. Critically, it has been theorized that IGEs constitute a large fitness target on which deleterious mutations can have pleiotropic effects, meaning that individuals carrying certain behavior-altering mutations can impose the fitness costs of those mutations on others comprising the broader social genome. Experimental data involving a mouse model support the existence of these IGE-amplified fitness losses; however, the underlying biological mechanisms that facilitate these remain unknown. In a mouse model of IGEs, we demonstrate that the Major Urinary Protein 20 pheromone, also called Darcin, produced by mice lacking the adhesion protein Neuroligin-3 acts as a vector to deleteriously modify the social behavior of wild-type mice. Additionally, we showed that lack of social interest on the part of Neuroligin-3 knockout mice is independent of their environment. These findings reveal a new role for mammalian pheromones in mediating the externalization of social deficits from one individual to others comprising the population through IGEs.Author SummaryIndirect genetic effects (IGEs) are mechanisms by which individuals of particular genotypes can influence the behavioral phenotype of individuals of different genotypes, sometimes disruptively, in instances where one member of the population carriers a deleterious behavior altering variant. Although disruptive IGEs have been demonstrated in mice, its underlying molecular and genetic mechanisms remain unknown. Using an IGEs mouse model, we demonstrated that the pheromone protein Major Urinary Protein 20, also named Darcin, is as a vector and target of social epistasis a specific type of IGEs. This finding reveals a new function for mammalian pheromones in mediating social epistasis to degrade group social behavior.

scholarly journals Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kohei Kitagawa ◽  
Kensuke Matsumura ◽  
Masayuki Baba ◽  
Momoka Kondo ◽  
Tomoya Takemoto ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Behavior ◽  
Mouse Model ◽  
Mouse Models ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
De Novo Mutation ◽  
Behavioral Deficits

AbstractAutism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.

scholarly journals Structural and functional brain-wide alterations in A350V Iqsec2 mutant mice displaying autistic-like behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniela Lichtman ◽  
Eyal Bergmann ◽  
Alexandra Kavushansky ◽  
Nadav Cohen ◽  
Nina S. Levy ◽  
...  
Keyword(s):  
Social Behavior ◽  
Functional Connectivity ◽  
Mouse Model ◽  
Ampa Receptor ◽  
Social Preference ◽  
Autism Spectrum ◽  
Receptor Trafficking ◽  
Anterior Cingulate ◽  
The Impact ◽  
Ampa Receptor Trafficking

AbstractIQSEC2 is an X-linked gene that is associated with autism spectrum disorder (ASD), intellectual disability, and epilepsy. IQSEC2 is a postsynaptic density protein, localized on excitatory synapses as part of the NMDA receptor complex and is suggested to play a role in AMPA receptor trafficking and mediation of long-term depression. Here, we present brain-wide structural volumetric and functional connectivity characterization in a novel mouse model with a missense mutation in the IQ domain of IQSEC2 (A350V). Using high-resolution structural and functional MRI, we show that animals with the A350V mutation display increased whole-brain volume which was further found to be specific to the cerebral cortex and hippocampus. Moreover, using a data-driven approach we identify putative alterations in structure–function relations of the frontal, auditory, and visual networks in A350V mice. Examination of these alterations revealed an increase in functional connectivity between the anterior cingulate cortex and the dorsomedial striatum. We also show that corticostriatal functional connectivity is correlated with individual variability in social behavior only in A350V mice, as assessed using the three-chamber social preference test. Our results at the systems-level bridge the impact of previously reported changes in AMPA receptor trafficking to network-level disruption and impaired social behavior. Further, the A350V mouse model recapitulates similarly reported brain-wide changes in other ASD mouse models, with substantially different cellular-level pathologies that nonetheless result in similar brain-wide alterations, suggesting that novel therapeutic approaches in ASD that result in systems-level rescue will be relevant to IQSEC2 mutations.

scholarly journals Aberrant aggressive behavior in a mouse model of Angelman syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lilach Simchi ◽  
Hanoch Kaphzan
Keyword(s):  
Social Behavior ◽  
Mouse Model ◽  
Aggressive Behavior ◽  
Social Interactions ◽  
Angelman Syndrome ◽  
Case Reports ◽  
Neurodevelopmental Disorder ◽  
Therapeutic Interventions ◽  
Affiliative Behavior ◽  
Severe Difficulty

AbstractAngelman syndrome (AS) is a genetic neurodevelopmental disorder due to the absence of the E3-ligase protein, UBE3A. Inappropriate social interactions, usually hyper-sociability, is a part of that syndrome. In addition, clinical surveys and case reports describe aggressive behavior in AS individuals as a severe difficulty for caretakers. A mouse model for AS recapitulates most of the human AS phenotypes. However, very few studies utilized this mouse model for investigating affiliative social behavior, and not even a single study examined aggressive behavior. Hence, the aim of the herein study was to examine affiliative and aggressive social behavior. For that, we utilized a battery of behavioral paradigms, and performed detailed analyses of these behaviors. AS mice exhibited a unique characteristic of reduced habituation towards a social stimulus in comparison to their wild-type (WT) littermates. However, overall there were no additional marked differences in affiliative social behavior. In contrast to the mild changes in affiliative behavior, there was a striking enhanced aggression in the AS mice compared to their WT littermates. The herein findings emphasize the use of AS mouse model in characterizing and measuring inappropriate aggressive behavior, and suggests these as tools for investigating therapeutic interventions aimed at attenuating aggressive behavior.

scholarly journals Belowground interactions shift the relative importance of direct and indirect genetic effects

2013 ◽  
Vol 3 (6) ◽  
pp. 1692-1701 ◽  
Author(s):  
Mark A. Genung ◽  
Joseph K. Bailey ◽  
Jennifer A. Schweitzer
Keyword(s):  
Genetic Effects ◽  
Relative Importance ◽  
Indirect Genetic Effects ◽  
Belowground Interactions

scholarly journals Developmental and behavioral phenotypes in a mouse model of DDX3X syndrome

2021 ◽  
Author(s):  
Andrea Boitnott ◽  
Marta Garcia-Forn ◽  
Dévina C. Ung ◽  
Kristi Niblo ◽  
Danielle Mendonca ◽  
...  
Keyword(s):  
Mouse Model ◽  
Behavioral Phenotypes

Major Urinary Protein Complex of Normal Mice: Origin

Science ◽  
1965 ◽  
Vol 149 (3687) ◽  
pp. 981-982 ◽  
Author(s):  
J. S. Finlayson ◽  
R. Asofsky ◽  
M. Potter ◽  
C. C. Runner
Keyword(s):  
Protein Complex ◽  
Urinary Protein ◽  
Major Urinary Protein

Modulation of behavioral phenotypes by a muscarinic M1 antagonist in a mouse model of fragile X syndrome

2011 ◽  
Vol 217 (1) ◽  
pp. 143-151 ◽  
Author(s):  
Surabi Veeraragavan ◽  
Nghiem Bui ◽  
Jennie R. Perkins ◽  
Lisa A. Yuva-Paylor ◽  
Randall L. Carpenter ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Behavioral Phenotypes

Pathogenicity of Candida tropicalis and Candida albicans after gastrointestinal inoculation in mice

1980 ◽  
Vol 29 (2) ◽  
pp. 808-813 ◽  
Author(s):  
J R Wingard ◽  
J D Dick ◽  
W G Merz ◽  
G R Sandford ◽  
R Saral ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mouse Model ◽  
Lung Tissue ◽  
Candida Tropicalis ◽  
Cytotoxic Drugs ◽  
Clinical Isolates ◽  
Yeast Cells ◽  
Gastrointestinal Mucosa ◽  
Compromised Host ◽  
Adult Mice

The ability of clinical isolates of Candida albicans and candida tropicalis to invade through normal and damaged gastrointestinal mucosa was determined. Adult mice were treated with either gentamicin or gentamicin and cytarabine. Suspensions of yeast cells (10(7)) were administered through a catheter intraesophageally. Invasion was determined by culturing liver, kidney, and lung tissue from mice sacrificed after 48 h. C. albicans and C. tropicalis were incapable of invading through normal gastrointestinal mucosa in mice treated only with gentamicin. Two isolates of C. tropicalis penetrated the damaged gastrointestinal mucosa in 69% (49 of 71) of mice treated with gentamicin and cytarabine. In contrast, three isolates of C. albicans penetrated he damaged gastrointestinal mucosa in only 23% (14 of 62) of mice. These results suggest that C. tropicalis is more capable of invading through damaged gastrointestinal mucosa than C. albicans. The observations in this mouse model parallel those seen in patients on cytotoxic drugs. Therefore, this model offers a tool for investigation of the pathogenicity of these organisms in a model analogous to the compromised host.

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