scholarly journals Sex-dependent parameters of social behavior show marked variations between distinct laboratory mouse strains and their mixed offspring

2021 ◽  
Author(s):  
Natalia Kopachev ◽  
Shai Netser ◽  
Shlomo Wagner
Keyword(s):  
Social Behavior ◽  
Social Preference ◽  
Laboratory Mouse ◽  
Preference Test ◽  
Autism Spectrum ◽  
Mouse Strains ◽  
Dependent Manner ◽  
Laboratory Mice ◽  
Novelty Preference ◽  
Behavioral Dynamics

Background: The survival of individuals of gregarious species depends on their ability to properly form social interactions. In humans, atypical social behavior is a hallmark of several psychopathological conditions, such as depression and autism spectrum disorder, many of which have sex-specific manifestations. Various strains of laboratory mice are used to reveal the mechanisms mediating typical and atypical social behavior in mammals. Methods: Here we used three social discrimination tests (social preference, social novelty preference, and sex preference) to characterize social behavior in males and females of three widely used laboratory mouse strains (C57BL/6J, BALB/c, and ICR). Results: We found marked sex- and strain-specific differences in the preference exhibited by subjects in a test-dependent manner. Interestingly, we found some characteristics that were strain-dependent, while others were sex-dependent. Moreover, even in the social preference test, where both sexes of all strains prefer social over object stimuli, we revealed sex- and strain-specific differences in the behavioral dynamics. We then cross-bred C57BL/6J and BALB/c mice and demonstrated that the offspring of such cross-breeding exhibit a profile of social behavior which is different from both parental strains and depends on the specific combination of parental strains. Conclusions: We conclude that social behavior of laboratory mice is highly sex- and strain-specific and strongly depends on genetic factors.

scholarly journals Distinct dynamics of social motivation drive differential social behavior in laboratory rat and mouse strains

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shai Netser ◽  
Ana Meyer ◽  
Hen Magalnik ◽  
Asaph Zylbertal ◽  
Shani Haskal de la Zerda ◽  
...  
Keyword(s):  
Social Behavior ◽  
Social Preference ◽  
Model Organism ◽  
Preference Test ◽  
Social Motivation ◽  
Mouse Strains ◽  
Sprague Dawley ◽  
Social Investigation ◽  
Sd Rats ◽  
Behavioral Studies

AbstractMice and rats are widely used to explore mechanisms of mammalian social behavior in health and disease, raising the question whether they actually differ in their social behavior. Here we address this question by directly comparing social investigation behavior between two mouse and rat strains used most frequently for behavioral studies and as models of neuropathological conditions: C57BL/6 J mice and Sprague Dawley (SD) rats. Employing novel experimental systems for behavioral analysis of both subjects and stimuli during the social preference test, we reveal marked differences in behavioral dynamics between the strains, suggesting stronger and faster induction of social motivation in SD rats. These different behavioral patterns, which correlate with distinctive c-Fos expression in social motivation-related brain areas, are modified by competition with non-social rewarding stimuli, in a strain-specific manner. Thus, these two strains differ in their social behavior, which should be taken into consideration when selecting an appropriate model organism.

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 t-Specific DNA polymorphisms among wild mice from Israel and Spain.

Genetics ◽  
1988 ◽  
Vol 119 (1) ◽  
pp. 157-160
Author(s):  
F Figueroa ◽  
E Neufeld ◽  
U Ritte ◽  
J Klein
Keyword(s):  
Laboratory Mouse ◽  
The Other ◽  
Dna Polymorphisms ◽  
Chromosome 17 ◽  
Mouse Strains ◽  
Laboratory Mice ◽  
Wild Type ◽  
Wild Mice ◽  
T Complex ◽  
Length Polymorphisms

Abstract Lehrach and his coworkers have isolated a series of DNA probes that specifically hybridize with different regions of mouse chromosome 17 within the t complex. The probes display restriction fragment length polymorphisms, RFLPs, which are specific for the t haplotypes in all laboratory mouse strains tested thus far. Some of these probes have been used to test wild mice populations for these t-associated DNA forms. It is demonstrated that populations from Germany, Switzerland, Italy, Greece, Yugoslavia, Australia, Costa Rica, and Venezuela contain chromosomes in which all the tested DNA loci display the t-specific polymorphisms. The frequency of mice carrying these chromosomes is as high as 31%. Wild mice from Israel and Spain, on the other hand, carry chromosomes displaying t-specific DNA forms only at one or two of the probed loci, while the other loci carry the wild-type (+) forms. These chromosomes thus resemble the partial t haplotypes known from the study of laboratory mice. One possible interpretation of these findings is that these DNA polymorphisms contributed to the assembly of the complete t haplotypes and that these haplotypes may have originated in the Middle East.

scholarly journals Cerebellar modulation of the reward circuitry and social behavior

Science ◽  
2019 ◽  
Vol 363 (6424) ◽  
pp. eaav0581 ◽  
Author(s):  
Ilaria Carta ◽  
Christopher H. Chen ◽  
Amanda L. Schott ◽  
Schnaude Dorizan ◽  
Kamran Khodakhah
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Behavior ◽  
Mental Disorders ◽  
Ventral Tegmental Area ◽  
Social Preference ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Reward Circuitry ◽  
The Social ◽  
The Brain

The cerebellum has been implicated in a number of nonmotor mental disorders such as autism spectrum disorder, schizophrenia, and addiction. However, its contribution to these disorders is not well understood. In mice, we found that the cerebellum sends direct excitatory projections to the ventral tegmental area (VTA), one of the brain regions that processes and encodes reward. Optogenetic activation of the cerebello-VTA projections was rewarding and, in a three-chamber social task, these projections were more active when the animal explored the social chamber. Intriguingly, activity in the cerebello-VTA pathway was required for the mice to show social preference in this task. Our data delineate a major, previously unappreciated role for the cerebellum in controlling the reward circuitry and social behavior.

scholarly journals Erroneous inference based on a lack of preference within one group: autism, mice, and the Social Approach Task

2019 ◽  
Author(s):  
Kayla R. Nygaard ◽  
Susan E. Maloney ◽  
Joseph D. Dougherty
Keyword(s):  
Social Behavior ◽  
Analytical Approach ◽  
Social Preference ◽  
Original Data ◽  
Autism Spectrum ◽  
False Positives ◽  
Simple Solution ◽  
Social Approach ◽  
The Social ◽  
Significant Difference

AbstractThe Social Approach Task is commonly used to identify sociability deficits when modeling liability factors for autism spectrum disorder (ASD) in mice. It was developed to expand upon assays available to examine distinct aspects of social behavior in rodents and has become a standard component of mouse ASD-relevant phenotyping pipelines. However, there is variability in the statistical analysis and interpretation of results from this task. A common analytical approach is to conduct within-group comparisons only, and then interpret a difference in significance levels as if it were a group difference, without any direct comparison. As an efficient shorthand, we named this approach EWOCs:Erroneous Within-group Only Comparisons. Here we examined the prevalence of EWOCs and used simulations to test whether it could produce misleading inferences. Our review of Social Approach studies of high-confidence ASD genes revealed 45% of papers sampled used only this analytical approach. Through simulations, we then demonstrate how a lack of significant difference within one group often doesn’t correspond to a significant difference between groups, and show this erroneous interpretation increases the rate of false positives up to 25%. Finally, we define a simple solution: use an index, like a social preference score, with direct statistical comparisons between groups to identify significant differences. We also provide power calculations to guide sample size in future studies. Overall, elimination of EWOCs and adoption of direct comparisons should result in more accurate, reliable, and reproducible data interpretations from the Social Approach Task across ASD liability models.Lay SummaryThe Social Approach Task is widely used to assess social behavior in mice and is frequently used in studies modeling autism. However, reviewing published studies showed nearly half do not use correct comparisons to interpret the data. Using simulated and original data, we argue the correct statistical approach is a direct comparison of scores between groups. This simple solution should reduce false positives and improve consistency of results across studies.

scholarly journals β-catenin signaling via astrocyte-encoded TCF7L2 regulates neuronal excitability and social behavior

2020 ◽  
Author(s):  
Szewczyk Lukasz Mateusz ◽  
Lipiec Marcin Andrzej ◽  
Liszewska Ewa ◽  
Urban-Ciecko Joanna ◽  
Kondrakiewicz Ludwika ◽  
...  
Keyword(s):  
Social Behavior ◽  
Wnt Signaling ◽  
Neuronal Excitability ◽  
Neuronal Development ◽  
Social Preference ◽  
Synapse Formation ◽  
Autism Spectrum ◽  
Postnatal Period ◽  
Conditional Knockout ◽  
Canonical Wnt

AbstractAstrocytes play essential roles in supporting neuronal activity and synapse formation; however, mechanisms by which these functions are regulated are unclear. The Wnt/β-catenin signaling pathway plays a crucial role in brain development and is implicated in neurodevelopmental disorders including autism spectrum disorder (ASD). We sought to investigate if some impacts of Wnt signaling are mediated via astrocytes. Here we show that the canonical Wnt/β-catenin pathway is active in postnatal cortical astrocytes and that its effector, the transcription factor TCF7L2 –is expressed in astrocyte lineage cells during embryonic and postnatal development in both mouse and human. Astrocyte-specific deletion of Tcf7l2 in the early postnatal period led to alterations in astrocyte morphology, membrane depolarization and decreased cortical neuron excitability. Mice with the conditional knockout exhibited increased sociability and social preference in a naturalistic setting. Taken together, these data reveal a key role of astrocytic Wnt signaling in shaping postnatal neuronal development and adult social behavior.

scholarly journals Adolescent sleep is critical for the developmental shaping of social novelty preference

2020 ◽  
Author(s):  
Wen-Jie Bian ◽  
Luis de Lecea
Keyword(s):  
Social Interaction ◽  
Social Behavior ◽  
Sleep Problems ◽  
Critical Role ◽  
Sleep Onset ◽  
Young Patients ◽  
Autism Spectrum ◽  
Sleep Disruption ◽  
Novelty Preference ◽  
Adolescent Sleep

AbstractSleep takes one-third of our lives, yet its functions remain largely unknown. A large proportion of young patients with neurodevelopmental disorders such as autism spectrum disorders (ASDs) and schizophrenia have sleep problems, including delayed sleep onset, shortened sleep duration and sleep fragmentation, which have been linked to social interaction deficit, a shared symptom of these disorders. However, the causal relationship between sleep disruption and social defects as well as the underlying mechanisms have not yet been established despite its importance in understanding the etiology of these disorders and developing potential therapeutic means. Here using the three-chamber social interaction test, we found that developmental sleep disruption (SD) in adolescent mice caused significant and long-lasting impairment in the preference towards social novelty during adult social interactions without affecting the overall sociality. Interestingly, SD performed in the adulthood did not induce any social defect, indicating a critical period within adolescence during which sleep shapes social novelty preference. Furthermore, by analyzing the adolescent sleep and adult social behavior in a mouse model of Shank3 mutation that mimics a genetic aberrance in ASDs, we found that the development of sociality is correlated with adolescent NREM sleep while social novelty preference is correlated with adolescent REM sleep. Collectively, these results demonstrate a critical role of adolescent sleep in the forming of social novelty preference and the developmental shaping of social behavior.

Homology of p53 intronic sequences between four laboratory mouse strains and Japanese wild mouse (Mus musculus molossinus Mishima)

Genome ◽  
1994 ◽  
Vol 37 (6) ◽  
pp. 1022-1026 ◽  
Author(s):  
Masayuki Tokumitsu ◽  
Katsuhiro Ogawa
Keyword(s):  
Loss Of Heterozygosity ◽  
Mus Musculus ◽  
Laboratory Mouse ◽  
Wild Mouse ◽  
P53 Gene ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Restriction Enzyme Digestion ◽  
Laboratory Mice ◽  
Wild Mice

Strain variation in the mouse p53 gene sequences was investigated in various regions of the gene in 14 inbred strains of laboratory mice and one Japanese wild mouse strain (Mus musculus molossinus Mishima, M. MOL-MSM). Nucleotides within p53 introns 1 and 7, found to be identical in 10 of the laboratory strains (129/J, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, CBA/J, CE/J, NZB, and SWR/J), were substituted for other nucleotide sequences in common with M. MOL-MSM and the four other strains (DBA/1J, DBA/2J, I/LnJ, and P/J). The latter were documented to have originated from a common ancestor. These observations thus suggested the possibility that the p53 gene may have become substituted by outcrossing of this ancestral strain with Asian mice; this is presumably related to the documentation that Japanese mice brought to western countries were used as laboratory mice early in this century. To establish p53 gene heterozygosity, female C3H/HeJ and male DBA/2J mice were mated to produce F1, hybrids (C3D2F1,). Electrophoresis of PCR fragments including polymorphic regions with or without restriction enzyme digestion, allowed clear distinction of paternal and maternal p53 alleles. These markers, therefore, should be useful for studying the loss of heterozygosity of the p53 gene during the carcinogenic process.Key words: p53 gene, polymorphism, Japanese wild mice, laboratory mice, loss of heterozygosity.

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