In humans a chromosomal hemideletion of the 16p11.2 region results in variable neurodevelopmental deficits including developmental delay, intellectual disability, and features of autism spectrum disorder (ASD). Serotonin is implicated in ASD but its role remains enigmatic. In this study we sought to determine if and how abnormalities in serotonin neurotransmission could contribute to the behavioral phenotype of the 16p11.2 deletion syndrome in a mouse model (Del mouse). As ASD is frequently associated with altered response to acute stress and stress may exacerbate repetitive behavior in ASD, we studied the Del mouse behavior in the context of an acute stress using the forced swim test, a paradigm well characterized with respect to serotonin. Del mice perseverated with active coping (swimming) in the forced swim test and failed to adopt passive coping strategies with time as did their wild-type littermates. Analysis of monoamine content by HPLC provided evidence for altered endogenous serotonin neurotransmission in Del mice while there was no effect of genotype on any other monoamine. Moreover, we found that Del mice were highly sensitive to the 5-HT2A antagonists M100907, which at a dose of 0.1 mg/kg normalized their level of active coping and restored the gradual shift to passive coping in the forced swim test. Supporting evidence for altered endogenous serotonin signaling was provided by observations of additional ligand effects including altered forebrain Fos expression. Taken together, these observations indicate notable changes in endogenous serotonin signaling in 16p11.2 deletion mice and support the therapeutic utility of 5-HT2A receptor antagonists.
Pubmed ID: 28948999 RIS Download
Mesh terms: Adaptation, Psychological | Animals | Autistic Disorder | Behavior, Animal | Chromosome Deletion | Chromosome Disorders | Chromosomes, Human, Pair 16 | Disease Models, Animal | Fluorobenzenes | Intellectual Disability | Male | Mice | Piperidines | Receptor, Serotonin, 5-HT2A | Serotonin | Serotonin 5-HT2 Receptor Antagonists | Stress, Psychological
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
These Brainbow 1.0 (founder line L) mice allow labeling of individual neuronal types (specifically hippocampal neuron cell bodies, and including motor neurons, dentate gyrus granule cells, pyramidal neurons of the cortex and CA1 area) with approximately 166 distinguishable color variations in cre recombined cells, and may also be useful in conjunction with other Brainbow strains (Stock No. 007901, Stock No. 007911, Stock No. 007921) for neurobiological studies. These Thy1-Brainbow 1.0 (line L) transgenic mice are viable and fertile. The mice possess multiple fluorescent protein sequences uniquely flanked with pairs of incompatible Lox sites alternated to create mutually exclusive recombination events; allowing stochastic expression of multiple fluorescent proteins from a single transgene. Prior to Cre-mediated recombination, the fluorescent protein immediately adjacent to the promoter, dTomato (RFP), is expressed in peripheral and central neurons. When bred to Cre recombinase expressing mice, the resulting offspring can have one of three expression outcomes for each transgene in each cell of the cre expressing tissue(s): dTomato (RFP) (no recombination), mCerulean (CFP), or mYFP. Integration of tandem transgene copies yields combinatorial fluorescent protein expression in each cell, and thus many possible cell colors, providing a way to distinguish adjacent neurons and visualize other cellular interactions. Of note, the single FRT site inserted in the transgene allows tandem transgene copy number reduction through Flp-mediated recombination if desired. These Brainbow 1.0 (founder line L) mice were found to have multiple transgene copies that allow labeling of individual neuronal types (specifically hippocampal neuron cell bodies, and including motor neurons, dentate gyrus granule cells, pyramidal neurons of the cortex and CA1 area) with approximately 166 distinguishable color variations in cre recombined cells, and may also be useful in conjunction with other Brainbow strains (Stock No. 007901, Stock No. 007911, Stock No. 007921) for neurobiological studies. This mouse can be used to support research in many areas including:
* Cre-lox System (loxP-flanked Sequences)
* Fluorescent protein expression in neural tissue
* Cre-lox-System (loxP-flanked Sequences: Test/Reporter)
* Developmental Biology Research (Cre-lox system)
* Developmental Biology Research (transplantation marker for embryonic and adult tissue)
* FLP-FRT System (FRT-flanked Sequences)
* Fluorescent Proteins * Genetics Research (Mutagenesis and Transgenesis: Cre-lox system) * Genetics Research (Tissue/Cell Markers: Cre-lox system) * Genetics Research (Tissue/Cell Markers: astrocyte-specific marker) * Genetics Research (Tissue/Cell Markers: astrocytes) * Genetics Research (Tissue/Cell Markers: astrocytes, neurons) * Genetics Research (Tissue/Cell Markers: glial cells) * Genetics Research (Tissue/Cell Markers: multiple) * Genetics Research (Tissue/Cell Markers: neurons) * Genetics Research (Tissue/Cell Markers: transplantation marker for embryonic and adult tissue) * Neurobiology Research (astrocyte-specific marker) * Neurobiology Research (cell marker) * YFP related Research Tools * Fluorescent Proteins Control: 000664 C57BL/6J (approximate)
toolView all literature mentions
Non profit, private research and education institution that performs molecular and genetic research used to generate methods for better diagnostics and treatments for cancer and neurological diseases. Research of cancer causing genes and their respective signaling pathways, mutations and structural variations of the human genome that could cause neurodevelopmental and neurodegenerative illnesses such as autism, schizophrenia, and Alzheimer's and Parkinson's diseases and also research in plant genetics and quantitative biology.
toolView all literature mentions