Using Knockout and Transgenic Mice to Study Neurophysiology and Behavior

1998 ◽  
Vol 78 (4) ◽  
pp. 1131-1163 ◽  
Author(s):  
MARINA R. PICCIOTTO ◽  
KEVIN WICKMAN

Picciotto, Marina R., and Kevin Wickman. Using Knockout and Transgenic Mice to Study Neurophysiology and Behavior. Physiol. Rev. 78: 1131–1163, 1998. — Reverse genetics, in which detailed knowledge of a gene of interest permits in vivo modification of its expression or function, provides a powerful method for examining the physiological relevance of any protein. Transgenic and knockout mouse models are particularly useful for studies of complex neurobiological problems. The primary aims of this review are to familiarize the nonspecialist with the techniques and limitations of mouse mutagenesis, to describe new technologies that may overcome these limitations, and to illustrate, using representative examples from the literature, some of the ways in which genetically altered mice have been used to analyze central nervous system function. The goal is to provide the information necessary to evaluate critically studies in which mutant mice have been used to study neurobiological problems.

2022 ◽  
Vol 15 ◽  
Author(s):  
Krissy A. Lyon ◽  
Nicola J. Allen

Astrocytes are non-neuronal cells that regulate synapses, neuronal circuits, and behavior. Astrocytes ensheath neuronal synapses to form the tripartite synapse where astrocytes influence synapse formation, function, and plasticity. Beyond the synapse, recent research has revealed that astrocyte influences on the nervous system extend to the modulation of neuronal circuitry and behavior. Here we review recent findings on the active role of astrocytes in behavioral modulation with a focus on in vivo studies, primarily in mice. Using tools to acutely manipulate astrocytes, such as optogenetics or chemogenetics, studies reviewed here have demonstrated a causal role for astrocytes in sleep, memory, sensorimotor behaviors, feeding, fear, anxiety, and cognitive processes like attention and behavioral flexibility. Current tools and future directions for astrocyte-specific manipulation, including methods for probing astrocyte heterogeneity, are discussed. Understanding the contribution of astrocytes to neuronal circuit activity and organismal behavior will be critical toward understanding how nervous system function gives rise to behavior.


2002 ◽  
Vol 11 (3) ◽  
pp. 253-262 ◽  
Author(s):  
Branimir Cvetkovic ◽  
Henry L. Keen ◽  
Xiaoji Zhang ◽  
Deborah Davis ◽  
Baoli Yang ◽  
...  

Angiotensinogen (AGT) was the first gene to be genetically linked to hypertension in humans. Analysis of the gene sequence identified a number of polymorphisms, several of which were reported associated with increased blood pressure (BP) or other cardiovascular diseases. One haplotype of the human AGT (hAGT) gene consisting of an allele at the −6 (A vs. G) position in the promoter and the sequence encoding amino acid 235 (Thr vs. Met) attracted the most attention and has been the subject of numerous association studies. In this report, we addressed the physiological relevance of alleles at these two positions using an experimental mouse model system. Transgenic mice were generated by targeting each haplotype [−6G/235Met (GM) and −6A/235Thr (AT)] as a single copy transgene to the mouse hypoxanthine phosphoribosyl transferase locus, allowing direct comparison of the two transgenes in vivo. Our results indicate that both transgenes exhibit the same transcriptional activity and produce similar levels of hAGT protein in the plasma of the transgenic mice. BP analysis was performed in double transgenic mice generated by breeding each hAGT line to mice expressing a human renin gene. A small but significant increase in BP and relative heart weight was demonstrated by mice carrying the GM haplotype. Moreover, compensatory downregulation of endogenous renin expression was more pronounced in mice containing the GM variant. Our findings suggest that the AT and GM haplotypes of the hAGT gene have no effect on gene expression, but may affect the cardiovascular system and the regulation of BP differently.


2021 ◽  
Author(s):  
Jessica L Sevetson ◽  
Brian Theyel ◽  
Diane Hoffman-Kim

Three-dimensional brain cultures can facilitate the study of central nervous system function and disease, and one of the most important components that they present is neuronal activity on a network level. Here we demonstrate network activity in rodent cortical spheroids while maintaining the networks intact in their 3D state. Networks developed by nine days in culture and became more complex over time. To measure network activity, we imaged neurons in rat and mouse spheroids labelled with a calcium indicator dye, and in mouse spheroids expressing GCaMP. Network activity was evident when we electrically stimulated spheroids, was abolished with glutamatergic blockade, and was altered by GABAergic blockade or partial glutamatergic blockade. We quantified correlations and distances between somas with micron-scale spatial resolution. Spheroids seeded at as few as 4,000 cells gave rise to emergent network events, including oscillations. These results are the first demonstration that self-assembled rat and mouse spheroids exhibit network activity consistent with in vivo network events. These results open the door to experiments on neuronal networks that require fewer animals and enable high throughput experiments on network-perturbing alterations in neurons and glia.


2020 ◽  
Vol 64 (2) ◽  
pp. 251-261
Author(s):  
Jessica E. Fellmeth ◽  
Kim S. McKim

Abstract While many of the proteins involved in the mitotic centromere and kinetochore are conserved in meiosis, they often gain a novel function due to the unique needs of homolog segregation during meiosis I (MI). CENP-C is a critical component of the centromere for kinetochore assembly in mitosis. Recent work, however, has highlighted the unique features of meiotic CENP-C. Centromere establishment and stability require CENP-C loading at the centromere for CENP-A function. Pre-meiotic loading of proteins necessary for homolog recombination as well as cohesion also rely on CENP-C, as do the main scaffolding components of the kinetochore. Much of this work relies on new technologies that enable in vivo analysis of meiosis like never before. Here, we strive to highlight the unique role of this highly conserved centromere protein that loads on to centromeres prior to M-phase onset, but continues to perform critical functions through chromosome segregation. CENP-C is not merely a structural link between the centromere and the kinetochore, but also a functional one joining the processes of early prophase homolog synapsis to late metaphase kinetochore assembly and signaling.


GIS Business ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. 656-666
Author(s):  
Dr. Entisar Al-Obaidi

Media refers to the channels of communication through which we distribute news, education, movies, music, advertising messages and other information. It includes physical and online newspapers and magazines, television, radio, telephone, the Internet, fax and billboards, are a dominant force in lives of children. Although television is remaining the predominant medium for children and adolescents, the new technologies are become more popular. We have to concern about the potential harmful effects of media "messages and images"; however, the positive and negative effects of media should be recognized. Parents have to establish the plan for all media in family home. Media that are influences on children should be recognized by "schools, policymakers, product advertisers, and entertainment producers".


2020 ◽  
Vol 22 (12) ◽  
pp. 5-9
Author(s):  
Livak N.S. ◽  
Klimova I.V. ◽  
Lebedikhin V.V.

Modern youth and the student community today play a key role in the development of social and social life. Due to the peculiarities of the university space, the student community is in constant interaction and communication, both in the framework of the educational process and events of various formats, and in social and everyday conditions. In the context of interactions, this social group, which is most at risk of spreading negative ideologies that threaten not only the personal security of everyone, but also peaceful coexistence in the conditions of a multinational society in Russia. In the absence of educational measures as a prevention, an unfavorable environment arises in which it is very easy to influence the thinking of young people, their involvement in nationalist movements, extremist activities, etc. Hence the concept of «youth extremism» appears, which is manifested in the views and behavior of young people based on the manifestation of aggression and non-acceptance of dissenters. The search for new technologies of psychological support that allow to form cultural tolerance, value orientations and prevent the spread of extremist ideologies becomes relevant. The authors consider a set of measures that contribute to the generalization, dissemination, as well as the introduction into the student environment of the best practices of spiritual and moral education, the development of interethnic and interreligious dialogue, and the prevention of negative ideologies. To implement these tasks, it is necessary to form a pool of specialists in the prevention of extremism in the student environment, hold seminars and meetings for vice-rectors of universities on security and educational work, as well as educational seminars for managers of student organizations. This will make it possible to form leadership student associations that broadcast the values of cultural tolerance to the youth environment.


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