Toward Understanding the Diverse Roles of Perisomatic Interneurons in Epilepsy

Epileptic seizures are associated with excessive neuronal spiking. Perisomatic γ-aminobutyric acid (GABA)ergic interneurons specifically innervate the subcellular domains of postsynaptic excitatory cells that are critical for spike generation. With a revolution in transcriptomics-based cell taxonomy driving the development of novel transgenic mouse lines, selectively monitoring and modulating previously elusive interneuron types is becoming increasingly feasible. Emerging evidence suggests that the three types of hippocampal perisomatic interneurons, axo-axonic cells, along with parvalbumin- and cholecystokinin-expressing basket cells, each follow unique activity patterns in vivo, suggesting distinctive roles in regulating epileptic networks.

Download Full-text

Transmission of tauopathy strains is independent of their isoform composition

Nature Communications ◽

10.1038/s41467-019-13787-x ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 13

Author(s):

Zhuohao He ◽

Jennifer D. McBride ◽

Hong Xu ◽

Lakshmi Changolkar ◽

Soo-jung Kim ◽

...

Keyword(s):

Human Brain ◽

Transgenic Mouse ◽

Mouse Line ◽

Cell Type ◽

Transgenic Mouse Line ◽

Adult Human ◽

Tau Isoforms ◽

Underlying Mechanisms ◽

Mouse Lines

AbstractThe deposition of pathological tau is a common feature in several neurodegenerative tauopathies. Although equal ratios of tau isoforms with 3 (3R) and 4 (4R) microtubule-binding repeats are expressed in the adult human brain, the pathological tau from different tauopathies have distinct isoform compositions and cell type specificities. The underlying mechanisms of tauopathies are unknown, partially due to the lack of proper models. Here, we generate a new transgenic mouse line expressing equal ratios of 3R and 4R human tau isoforms (6hTau mice). Intracerebral injections of distinct human tauopathy brain-derived tau strains into 6hTau mice recapitulate the deposition of pathological tau with distinct tau isoform compositions and cell type specificities as in human tauopathies. Moreover, through in vivo propagation of these tau strains among different mouse lines, we demonstrate that the transmission of distinct tau strains is independent of strain isoform compositions, but instead intrinsic to unique pathological conformations.

Download Full-text

Real-time monitoring of stress erythropoiesis in vivo using Gata1 and β-globin LCR luciferase transgenic mice

Blood ◽

10.1182/blood-2005-10-4064 ◽

2006 ◽

Vol 108 (2) ◽

pp. 726-733 ◽

Cited By ~ 19

Author(s):

Mikiko Suzuki ◽

Kinuko Ohneda ◽

Sakie Hosoya-Ohmura ◽

Saho Tsukamoto ◽

Osamu Ohneda ◽

...

Keyword(s):

Real Time ◽

Transgenic Mouse ◽

Molecular Mechanisms ◽

Real Time Monitoring ◽

Erythroid Progenitors ◽

Stress Erythropoiesis ◽

Important Means ◽

As Stress ◽

Mouse Lines

Erythroid progenitors have the potential to proliferate rapidly in response to environmental stimuli. This process is referred to as stress erythropoiesis, with erythropoietin (EPO) playing central roles in its promotion. In this study, we wanted to elucidate the molecular mechanisms governing the regulation of stress erythropoiesis and the maintenance of red-cell homeostasis. This was achieved by our development of a noninvasive real-time monitoring system for erythropoiesis using transgenic mouse lines expressing luciferase under the control of the mouse Gata1 hematopoietic regulatory domain (G1-HRD-luc) or human β-globin locus control region (Hbb-LCR-luc). Optical bioluminescence images revealed that the luciferase was specifically expressed in spleen and bone marrow and was induced rapidly in response to anemia and hypoxia stimuli. The G1-HRD-luc activity tracked the emergence and disappearance of proerythroblast-stage progenitors, whereas the Hbb-LCR-luc activity tracked erythroblasts and later stage erythroid cells. Increased plasma EPO concentration preceded an increase in G1-HRD-luc, supporting our contention that EPO acts as the key upstream signal in stress erythropoiesis. Hence, we conclude that G1-HRD-luc and Hbb-LCR-luc reporters are differentially activated during stress erythropoiesis and that the transgenic mouse lines used serve as an important means for understanding the homeostatic regulation of erythropoiesis.

Download Full-text

Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines

10.1101/138511 ◽

2017 ◽

Author(s):

Nicholas A. Steinmetz ◽

Christina Buetfering ◽

Jerome Lecoq ◽

Christian R. Lee ◽

Andrew J. Peters ◽

...

Keyword(s):

Transgenic Mouse ◽

Activity Patterns ◽

Neuronal Responses ◽

Interictal Spikes ◽

Calcium Sensors ◽

Generalized Seizures ◽

Affected Mouse ◽

Underlying Mechanisms ◽

And Behavior ◽

Mouse Lines

AbstractTransgenic mouse lines are invaluable tools for neuroscience but as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically-encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, though rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

Download Full-text

Survivin overexpression alone does not alter megakaryocyte ploidy nor interfere with erythroid/megakaryocytic lineage development in transgenic mice

Blood ◽

10.1182/blood-2007-11-122150 ◽

2008 ◽

Vol 111 (8) ◽

pp. 4092-4095 ◽

Cited By ~ 10

Author(s):

Donald J. McCrann ◽

Todd Yezefski ◽

Hao G. Nguyen ◽

Nicholas Papadantonakis ◽

Hui Liu ◽

...

Keyword(s):

Transgenic Mouse ◽

Ploidy Level ◽

Survivin Expression ◽

Transgenic Mouse Models ◽

Protein Overexpression ◽

Vitro Data ◽

In Vitro Data ◽

Mouse Lines

Abstract The level of survivin was reported to be scarce in mouse megakaryocytes (MKs) compared with erythroid cells. Considering this finding and previously reported in vitro data showing decreased MK ploidy upon retroviral-mediated overexpression of survivin, we sought to examine whether ectopic survivin expression in the MK lineage might alter ploidy level in vivo. Here we report the generation of 2 tissue specific hematopoietic transgenic mouse models, one expressing survivin in both the erythroid and MK lineages and the other expressing survivin solely in the MK lineage. Survivin protein overexpression was confirmed in MKs and erythrocytes. Surprisingly, analysis of both transgenic mouse lines showed no detectable changes in MK number, ploidy level, and platelet and erythrocyte counts, as compared with control mice. We conclude that elevated survivin expression does not alter MK/erythroid lineage development and that elevated survivin, alone, does not interfere with MK ploidy in vivo.

Download Full-text

In vivo requirement of the α-syntrophin PDZ domain for the sarcolemmal localization of nNOS and aquaporin-4

The Journal of Cell Biology ◽

10.1083/jcb.200106158 ◽

2001 ◽

Vol 155 (1) ◽

pp. 113-122 ◽

Cited By ~ 123

Author(s):

Marvin E. Adams ◽

Heather A. Mueller ◽

Stanley C. Froehner

Keyword(s):

Transgenic Mouse ◽

Pdz Domain ◽

Full Length ◽

Aquaporin 4 ◽

Mdx Mouse ◽

Null Mouse ◽

Oxide Synthase ◽

Mouse Lines

α-Syntrophin is a scaffolding adapter protein expressed primarily on the sarcolemma of skeletal muscle. The COOH-terminal half of α-syntrophin binds to dystrophin and related proteins, leaving the PSD-95, discs-large, ZO-1 (PDZ) domain free to recruit other proteins to the dystrophin complex. We investigated the function of the PDZ domain of α-syntrophin in vivo by generating transgenic mouse lines expressing full-length α-syntrophin or a mutated α-syntrophin lacking the PDZ domain (ΔPDZ). The ΔPDZ α-syntrophin displaced endogenous α- and β1-syntrophin from the sarcolemma and resulted in sarcolemma containing little or no syntrophin PDZ domain. As a consequence, neuronal nitric oxide synthase (nNOS) and aquaporin-4 were absent from the sarcolemma. However, the sarcolemmal expression and distribution of muscle sodium channels, which bind the α-syntrophin PDZ domain in vitro, were not altered. Both transgenic mouse lines were bred with an α-syntrophin–null mouse which lacks sarcolemmal nNOS and aquaporin-4. The full-length α-syntrophin, not the ΔPDZ form, reestablished nNOS and aquaporin-4 at the sarcolemma of these mice. Genetic crosses with the mdx mouse showed that neither transgenic syntrophin could associate with the sarcolemma in the absence of dystrophin. Together, these data show that the sarcolemmal localization of nNOS and aquaporin-4 in vivo depends on the presence of a dystrophin-bound α-syntrophin PDZ domain.

Download Full-text

Voltage imaging using transgenic mouse lines expressing the GEVI ArcLight in two olfactory cell types

10.1101/2020.08.26.268904 ◽

2020 ◽

Author(s):

Jelena Platisa ◽

Hongkui Zeng ◽

Linda Madisen ◽

Lawrence B. Cohen ◽

Vincent A Pieribone ◽

...

Keyword(s):

Transgenic Mouse ◽

Granule Cells ◽

Signal To Noise Ratio ◽

Expression System ◽

Cell Types ◽

Mammalian Brain ◽

Voltage Imaging ◽

Genetic Tool ◽

Mouse Lines

AbstractGenetically encoded voltage indicators (GEVIs) allow for cell-specific optical recordings of membrane potential changes in defined cell populations. One tool that would further their use in the in vivo mammalian brain is transgenic reporter animals that facilitate precise and repeatable targeting with high expression levels. The present literature on the development and use of transgenic mouse lines as vehicles for GEVI expression is limited. Here we report the first in vivo experiments using a transgenic reporter mouse for the GEVI ArcLight (Ai86(TITL-ArcLight)), which utilizes a Cre/tTA dependent expression system (TIGRE 1.0). Following pairing to appropriate Cre- and tTA transgenic mice, we report two mouse lines with ArcLight expression restricted to olfactory sensory neurons (OMP-ArcLight), and a subpopulation of interneurons that include periglomerular and granule cells (Emx1-ArcLight) in the olfactory bulb (OB). The ArcLight expression in these lines was sufficient for in vivo imaging of odorant responses in single trials. Odor responses were measured in the OB using epifluorescence and 2-photon imaging. The voltage responses were odor-specific and concentration-dependent, and confirmed earlier conclusions from calcium measurements. This study shows that the ArcLight Ai86(TITL-ArcLight) transgenic line is a flexible genetic tool that can be used to record neuronal electrical activity of a variety of cell types with a signal-to-noise ratio that is comparable to previous reports using viral transduction.

Download Full-text

Recent advances in understanding basophil functions in vivo

F1000Research ◽

10.12688/f1000research.11697.1 ◽

2017 ◽

Vol 6 ◽

pp. 1464 ◽

Cited By ~ 10

Author(s):

David Voehringer

Keyword(s):

Transgenic Mouse ◽

Immune Cells ◽

Effector Cells ◽

The Past ◽

Helminth Infections ◽

Staining Techniques ◽

Immunomodulatory Properties ◽

And Function ◽

Mouse Lines

Basophils are mainly known as pro-inflammatory effector cells associated with allergy and helminth infections. Although they were identified over 130 years ago, their in vivo functions are still poorly understood. New insights into basophil development and function have been gained by the development of various transgenic mouse lines and staining techniques to detect and purify these cells from different organs. Several studies over the past few years have identified unexpected functions for basophils, including immunomodulatory properties and interactions with other immune cells. Here, I summarize and discuss the main findings.

Download Full-text