The Experts below are selected from a list of 13692 Experts worldwide ranked by ideXlab platform
Jacqueline N Crawley - One of the best experts on this subject based on the ideXlab platform.
-
Behavioral Phenotyping assays for genetic mouse models of neurodevelopmental neurodegenerative and psychiatric disorders
Annual Review of Animal Biosciences, 2017Co-Authors: Stacey Sukoff J Rizzo, Jacqueline N CrawleyAbstract:Animal models offer heuristic research tools to understand the causes of human diseases and to identify potential treatments. With rapidly evolving genetic engineering technologies, mutations identified in a human disorder can be generated in the mouse genome. Phenotypic outcomes of the mutation are then explicated to confirm hypotheses about causes and to discover effective therapeutics. Most neurodevelopmental, neurodegenerative, and psychiatric disorders are diagnosed primarily by their prominent Behavioral symptoms. Mouse Behavioral assays analogous to the human symptoms have been developed to analyze the consequences of mutations and to evaluate proposed therapeutics preclinically. Here we describe the range of mouse Behavioral tests available in the established Behavioral neuroscience literature, along with examples of their translational applications. Concepts presented have been successfully used in other species, including flies, worms, fish, rats, pigs, and nonhuman primates. Identical strategies can be employed to test hypotheses about environmental causes and gene × environment interactions.
-
Behavioral Phenotyping assays for genetic mouse models of neurodevelopmental neurodegenerative and psychiatric disorders
Annual Review of Animal Biosciences, 2017Co-Authors: Stacey Sukoff J Rizzo, Jacqueline N CrawleyAbstract:Animal models offer heuristic research tools to understand the causes of human diseases and to identify potential treatments. With rapidly evolving genetic engineering technologies, mutations identified in a human disorder can be generated in the mouse genome. Phenotypic outcomes of the mutation are then explicated to confirm hypotheses about causes and to discover effective therapeutics. Most neurodevelopmental, neurodegenerative, and psychiatric disorders are diagnosed primarily by their prominent Behavioral symptoms. Mouse Behavioral assays analogous to the human symptoms have been developed to analyze the consequences of mutations and to evaluate proposed therapeutics preclinically. Here we describe the range of mouse Behavioral tests available in the established Behavioral neuroscience literature, along with examples of their translational applications. Concepts presented have been successfully used in other species, including flies, worms, fish, rats, pigs, and nonhuman primates. Identical strategie...
-
sociability and motor functions in shank1 mutant mice
Brain Research, 2011Co-Authors: Jill L Silverman, Albert Y Hung, Charlotte L Barkan, Seda S Tolu, Sarah M Turner, Roheeni Saxena, Morgan Sheng, Jacqueline N CrawleyAbstract:Autism is a neurodevelopmental disorder characterized by aberrant reciprocal social interactions, impaired communication, and repetitive behaviors. While the etiology remains unclear, strong evidence exists for a genetic component, and several synaptic genes have been implicated. SHANK genes encode a family of synaptic scaffolding proteins located postsynaptically on excitatory synapses. Mutations in SHANK genes have been detected in several autistic individuals. To understand the consequences of SHANK mutations relevant to the diagnostic and associated symptoms of autism, comprehensive Behavioral Phenotyping on a line of Shank1 mutant mice was conducted on multiple measures of social interactions, social olfaction, repetitive behaviors, anxiety-related behaviors, motor functions, and a series of control measures for physical abilities. Results from our comprehensive Behavioral Phenotyping battery indicated that adult Shank1 null mutant mice were similar to their wildtype and heterozygous littermates on standardized measures of general health, neurological reflexes and sensory skills. Motor functions were reduced in the null mutants on open field activity, rotarod, and wire hang, replicating and extending previous findings (Hung et al., 2008). A partial anxiety-like phenotype was detected in the null mutants in some components of the light ↔ dark task, as previously reported (Hung et al., 2008) but not in the elevated plus-maze. Juvenile reciprocal social interactions did not differ across genotypes. Interpretation of adult social approach was confounded by a lack of normal sociability in wildtype and heterozygous littermates. All genotypes were able to discriminate social odors on an olfactory habituation/dishabituation task. All genotypes displayed relatively high levels of repetitive self-grooming. Our findings support the interpretation that Shank1 null mice do not demonstrate autism-relevant social interaction deficits, but confirm and extend a role for Shank1 in motor functions.
-
Behavioral Phenotyping Strategies for Mutant Mice
Neuron, 2008Co-Authors: Jacqueline N CrawleyAbstract:Comprehensive Behavioral analyses of transgenic and knockout mice have successfully identified the functional roles of many genes in the brain. Over the past 10 years, strategies for mouse Behavioral Phenotyping have evolved to maximize the scope and replicability of findings from a cohort of mutant mice, minimize the interpretation of procedural artifacts, and provide robust translational tools to test hypotheses and develop treatments. This Primer addresses experimental design issues and offers examples of high-throughput batteries, learning and memory tasks, and anxiety-related tests.
-
what s wrong with my mouse Behavioral Phenotyping of transgenic and knockout mice
2007Co-Authors: Jacqueline N CrawleyAbstract:array of choices available for assaying this Behavioral construct, and seeing that there are somewhat murky borders between the constructs ‘anxiety’, ‘fear’ and ‘depression’, he or she will explore the question further with an array of tests, after careful consideration of the idiosyncratic parameters required to elicit interpretable data from each test. Such attention to detail matters in real life, even when highly experienced Behavioral-testing laboratories are involved. For example, three groups recently independently produced null mutant mice for the corticotropinreleasing hormone 2 receptor. Each group was obviously interested in testing the effects of this gene deletion on anxiety. The results were published as three back-to-back-to-back papers in Nature Genetics 1‐3 . All three groups tested both male and female mice on a version of the elevated plus-maze anxiety test and reported their reluctance to enter open arms of the maze, the accepted index of anxiety. One group found no difference between knockout and wild type of either sex; one group found greater anxiety in knockouts of both sexes; and the third found greater anxiety in male knockouts only. All three also used an open field test, where reluctance to enter the center of the apparatus was the index of anxiety. Again, three different results were reported: one group found a tendency for greater anxiety in null mutants of both sexes; one found significantly greater anxiety in null mutants; and the third found that null mutant males (but not females) spent significantly more time in the center of the field, but interpreted the result to indicate greater anxiety! The different results could derive from many sources, including: differences in animal husbandry and handling before testing; relatively subtle differences in the test apparatus and test protocols; the specific genetic constructs inserted into embryonic stem cells; the stem-cell source strain (three different substrains of 129 inbred mice were used that are known to vary genetically 4
Tsuyoshi Miyakawa - One of the best experts on this subject based on the ideXlab platform.
-
comprehensive Behavioral Phenotyping of a new semaphorin 3 f mutant mouse
Molecular Brain, 2016Co-Authors: Tsuyoshi Miyakawa, Ikuo Matsuda, Hirotaka Shoji, Nobuyuki Yamasaki, Atsu AibaAbstract:Semaphorin 3 F (Sema3F) is a secreted type of the Semaphorin family of axon guidance molecules. Sema3F and its receptor neuropilin-2 (Npn-2) are expressed in a mutually exclusive manner in the embryonic mouse brain regions including olfactory bulb, hippocampus, and cerebral cortex. Sema3F is thought to have physiological functions in the formation of neuronal circuitry and its refinement. However, functional roles of Sema3F in the brain remain to be clarified. Here, we examined Behavioral effects of Sema3F deficiency through a comprehensive Behavioral test battery in Sema3F knockout (KO) male mice to understand the possible functions of Sema3F in the brain. Male Sema3F KO and wild-type (WT) control mice were subjected to a battery of Behavioral tests, including neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, social interaction, Porsolt forced swim, tail suspension, Barnes maze, and fear conditioning tests. In the open field test, Sema3F KO mice traveled shorter distance and spent less time in the center of the field than WT controls during the early testing period. In the light/dark transition test, Sema3F KO mice also exhibited decreased distance traveled, fewer number of transitions, and longer latency to enter the light chamber compared with WT mice. In addition, Sema3F KO mice traveled shorter distance than WT mice in the elevated plus maze test, although there were no differences between genotypes in open arm entries and time spent in open arms. Similarly, Sema3F KO mice showed decreased distance traveled in the social interaction test. Sema3F KO mice displayed reduced immobility in the Porsolt forced swim test whereas there was no difference in immobility between genotypes in the tail suspension test. In the fear conditioning test, Sema3F KO mice exhibited increased freezing behavior when exposed to a conditioning context and an altered context in absence of a conditioned stimulus. In the tests for assessing motor function, pain sensitivity, startle response to an acoustic stimulus, sensorimotor gating, or spatial reference memory, there were no significant Behavioral differences between Sema3F KO and WT mice. These results suggest that Sema3F deficiency induces decreased locomotor activity and possibly abnormal anxiety-related behaviors and also enhances contextual memory and generalized fear in mice. Thus, our findings suggest that Sema3F plays important roles in the development of neuronal circuitry underlying the regulation of some aspects of anxiety and fear responses.
-
synaptic e3 ligase scrapper in contextual fear conditioning extensive Behavioral Phenotyping of scrapper heterozygote and overexpressing mutant mice
PLOS ONE, 2011Co-Authors: Tsuyoshi Miyakawa, Keizo Takao, Ikuko Yao, Seiji Ito, Mitsutoshi SetouAbstract:SCRAPPER, an F-box protein coded by FBXL20, is a subunit of SCF type E3 ubiquitin ligase. SCRAPPER localizes synapses and directly binds to Rab3-interacting molecule 1 (RIM1), an essential factor for synaptic vesicle release, thus it regulates neural transmission via RIM1 degradation. A defect in SCRAPPER leads to neurotransmission abnormalities, which could subsequently result in neurodegenerative phenotypes. Because it is likely that the alteration of neural transmission in Scrapper mutant mice affect their systemic condition, we have analyzed the Behavioral phenotypes of mice with decreased or increased the amount of SCRAPPER. We carried out a series of Behavioral test batteries for Scrapper mutant mice. Scrapper transgenic mice overexpressing SCRAPPER in the hippocampus did not show any significant difference in every test argued in this manuscript by comparison with wild-type mice. On the other hand, heterozygotes of Scrapper knockout [SCR (+/−)] mice showed significant difference in the contextual but not cued fear conditioning test. In addition, SCR (+/−) mice altered in some tests reflecting anxiety, which implies the loss of functions of SCRAPPER in the hippocampus. The Behavioral phenotypes of Scrapper mutant mice suggest that molecular degradation conferred by SCRAPPER play important roles in hippocampal-dependent fear memory formation.
-
comprehensive Behavioral Phenotyping of ryanodine receptor type 3 ryr3 knockout mice decreased social contact duration in two social interaction tests
Frontiers in Behavioral Neuroscience, 2009Co-Authors: Naoki Matsuo, Keizo Takao, Nobuyuki Yamasaki, Koichi Tanda, Kazuo Nakanishi, Keiko Toyama, Hiroshi Takeshima, Tsuyoshi MiyakawaAbstract:Dynamic regulation of the intracellular Ca2+ concentration is crucial for various neuronal functions such as synaptic transmission and plasticity, and gene expression. Ryanodine receptors (RyRs) are a family of intracellular calcium release channels that mediate calcium-induced calcium release (CICR) from the endoplasmic reticulum. Among the three RyR isoforms, RyR3 is preferentially expressed in the brain especially in the hippocampus and striatum. To investigate the Behavioral effects of RyR3 deficiency, we subjected RyR3 knockout (RyR3-/-) mice to a battery of Behavioral tests. RyR3-/- mice exhibited significantly decreased social contact duration in two different social interaction tests, where two mice can freely move and make contacts with each other. They also exhibited hyperactivity and mildly impaired prepulse inhibition and latent inhibition while they did not show significant abnormalities in motor function and working and reference memory tests. These results suggest that RyR3 has an important role in locomotor activity and social behavior.
-
comprehensive Behavioral Phenotyping of calpastatin knockout mice
Molecular Brain, 2008Co-Authors: Ryuichi Nakajima, Nobuhisa Iwata, Shuming Huang, Jiro Takano, Tsuyoshi Miyakawa, Keizo TakaoAbstract:Background Calpastatin is an endogenous inhibitor of calpain, intracellular calcium-activated protease. It has been suggested to be involved in molecular mechanisms of long-term plasticity and excitotoxic pathways. However, functions of calpastatin in vivo are still largely unknown. To examine the physiological roles of calpastatin, we subjected calpastatin-knockout mice to a comprehensive Behavioral test battery.
Maria Luisa Scattoni - One of the best experts on this subject based on the ideXlab platform.
-
ultrasonic vocalizations as a fundamental tool for early and adult Behavioral Phenotyping of autism spectrum disorder rodent models
Neuroscience & Biobehavioral Reviews, 2020Co-Authors: Angela Caruso, Laura Ricceri, Maria Luisa ScattoniAbstract:Abstract In rodent models of Autism Spectrum Disorders (ASD), the study of ultrasonic vocalizations has provided the unique opportunity to evaluate social communication and interaction in ethologically-appropriate contexts, Behavioral domains relevant to the first core symptom of ASD. In the present review, we selected and evaluated ultrasonic vocalizations’ data collected in rodent models of ASD in different experimental settings, either in the neonatal phase or in adulthood. Both quantitative (calling rates) and qualitative (range and shape of the vocal repertoire) abnormalities have been evidenced. The aim of our work was to highlight several promises and a few caveats in the use of ultrasonic vocalizations for Behavioral Phenotyping of ASD models and give some suggestions to maximize the translational value of these studies.
Mitsutoshi Setou - One of the best experts on this subject based on the ideXlab platform.
-
synaptic e3 ligase scrapper in contextual fear conditioning extensive Behavioral Phenotyping of scrapper heterozygote and overexpressing mutant mice
PLOS ONE, 2011Co-Authors: Tsuyoshi Miyakawa, Keizo Takao, Ikuko Yao, Seiji Ito, Mitsutoshi SetouAbstract:SCRAPPER, an F-box protein coded by FBXL20, is a subunit of SCF type E3 ubiquitin ligase. SCRAPPER localizes synapses and directly binds to Rab3-interacting molecule 1 (RIM1), an essential factor for synaptic vesicle release, thus it regulates neural transmission via RIM1 degradation. A defect in SCRAPPER leads to neurotransmission abnormalities, which could subsequently result in neurodegenerative phenotypes. Because it is likely that the alteration of neural transmission in Scrapper mutant mice affect their systemic condition, we have analyzed the Behavioral phenotypes of mice with decreased or increased the amount of SCRAPPER. We carried out a series of Behavioral test batteries for Scrapper mutant mice. Scrapper transgenic mice overexpressing SCRAPPER in the hippocampus did not show any significant difference in every test argued in this manuscript by comparison with wild-type mice. On the other hand, heterozygotes of Scrapper knockout [SCR (+/−)] mice showed significant difference in the contextual but not cued fear conditioning test. In addition, SCR (+/−) mice altered in some tests reflecting anxiety, which implies the loss of functions of SCRAPPER in the hippocampus. The Behavioral phenotypes of Scrapper mutant mice suggest that molecular degradation conferred by SCRAPPER play important roles in hippocampal-dependent fear memory formation.
Laura Ricceri - One of the best experts on this subject based on the ideXlab platform.
-
ultrasonic vocalizations as a fundamental tool for early and adult Behavioral Phenotyping of autism spectrum disorder rodent models
Neuroscience & Biobehavioral Reviews, 2020Co-Authors: Angela Caruso, Laura Ricceri, Maria Luisa ScattoniAbstract:Abstract In rodent models of Autism Spectrum Disorders (ASD), the study of ultrasonic vocalizations has provided the unique opportunity to evaluate social communication and interaction in ethologically-appropriate contexts, Behavioral domains relevant to the first core symptom of ASD. In the present review, we selected and evaluated ultrasonic vocalizations’ data collected in rodent models of ASD in different experimental settings, either in the neonatal phase or in adulthood. Both quantitative (calling rates) and qualitative (range and shape of the vocal repertoire) abnormalities have been evidenced. The aim of our work was to highlight several promises and a few caveats in the use of ultrasonic vocalizations for Behavioral Phenotyping of ASD models and give some suggestions to maximize the translational value of these studies.
-
Behavioral Phenotyping of mouse models of neurodevelopmental disorders relevant social behavior patterns across the life span
Behavioural Brain Research, 2007Co-Authors: Laura Ricceri, Anna Moles, Jacqueline N CrawleyAbstract:Social responses are a key element for Behavioral Phenotyping of mouse models of neurodevelopmental disorders associated with social deficits. Here we describe selected Behavioral responses that can be measured in developing and adult mice, with special emphasis on ultrasonic vocalizations, a Behavioral response not yet systematically characterized in most of the genetic mouse models of social abnormalities. A recently developed task to measure social approach relevant to the first core symptom of autism is highlighted. We also focus on those developmental factors, including litter size, litter composition, and early social milieu, that are often underestimated when measuring adult social behavior in mouse models of neurodevelopmental disorders. We present a summary of available data concerning social Behavioral responses in mice with targeted gene mutations. We conclude by suggesting that assessment of early Behavioral traits, and corresponding relationships with adult Behavioral profiles, could be a useful strategy to investigate mouse models of neurodevelopmental disorders associated with social deficits.