Faculty Opinions recommendation of Analysis of knock-out mice to determine the role of HPC-1/syntaxin 1A in expressing synaptic plasticity.

2006 ◽  
Author(s):  
Jane Sullivan
Keyword(s):  
Synaptic Plasticity ◽  
Syntaxin 1A ◽  
Knock Out ◽  
Knock Out Mice

scholarly journals Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xin Ding ◽  
Jin Wang ◽  
Miaoxin Huang ◽  
Zhangpeng Chen ◽  
Jing Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Knock Out ◽  
Classical Complement Pathway ◽  
Synaptic Remodeling ◽  
The Central Nervous System ◽  
System Activation ◽  
Knock Out Mice ◽  
Synaptic Pruning

AbstractMicroglia play a key role in regulating synaptic remodeling in the central nervous system. Activation of classical complement pathway promotes microglia-mediated synaptic pruning during development and disease. CD47 protects synapses from excessive pruning during development, implicating microglial SIRPα, a CD47 receptor, in synaptic remodeling. However, the role of microglial SIRPα in synaptic pruning in disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion of SIRPα results in decreased synaptic density. In human tissue, we observe that microglial SIRPα expression declines alongside the progression of Alzheimer’s disease. To investigate the role of SIRPα in neurodegeneration, we modulate the expression of microglial SIRPα in mouse models of Alzheimer’s disease. Loss of microglial SIRPα results in increased synaptic loss mediated by microglia engulfment and enhanced cognitive impairment. Together, these results suggest that microglial SIRPα regulates synaptic pruning in neurodegeneration.

scholarly journals Rescue of NMDAR-Dependent Synaptic Plasticity in Fmr1 Knock-Out Mice

2013 ◽  
Vol 25 (1) ◽  
pp. 271-279 ◽  
Author(s):  
C. A. Bostrom ◽  
N.- M. Majaess ◽  
K. Morch ◽  
E. White ◽  
B. D. Eadie ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Knock Out ◽  
Knock Out Mice

scholarly journals REST is a major negative regulator of endocrine differentiation during pancreas organogenesis

2021 ◽  
Author(s):  
Meritxell Rovira ◽  
Goutham Atla ◽  
Miguel Angel Maestro ◽  
Vane Grau ◽  
Javier García-Hurtado ◽  
...  
Keyword(s):  
Endocrine Cells ◽  
Negative Regulator ◽  
Β Cell ◽  
Knock Out ◽  
Endocrine Differentiation ◽  
Conditional Allele ◽  
Embryonic Pancreas ◽  
Pancreatic Endocrine Cells ◽  
Knock Out Mice

SUMMARYUnderstanding genomic regulatory mechanisms of pancreas differentiation is relevant to the pathophysiology of diabetes mellitus, and to the development of replacement therapies. Numerous transcription factors promote β cell differentiation, although less is known about negative regulators. Earlier epigenomic studies suggested that the transcriptional repressor REST could be a suppressor of endocrine gene programs in the embryonic pancreas. However, pancreaticRestknock-out mice failed to show increased numbers of endocrine cells, suggesting that REST is not a major regulator of endocrine differentiation. Using a different conditional allele that enables profound REST inactivation, we now observe a marked increase in the formation of pancreatic endocrine cells. REST inhibition also promoted endocrinogenesis in zebrafish and mouse early postnatal ducts, and induced β-cell specific genes in human adult duct-derived organoids. Finally, we define REST genomic programs that suppress pancreatic endocrine differentiation. These results establish a crucial role of REST as a negative regulator of pancreatic endocrine differentiation.

scholarly journals Anatomical, Physiological, and Pharmacological Characteristics of Histidine Decarboxylase Knock-Out Mice: Evidence for the Role of Brain Histamine in Behavioral and Sleep–Wake Control

2002 ◽  
Vol 22 (17) ◽  
pp. 7695-7711 ◽  
Author(s):  
Régis Parmentier ◽  
Hiroshi Ohtsu ◽  
Zahia Djebbara-Hannas ◽  
Jean-Louis Valatx ◽  
Takehiko Watanabe ◽  
...  
Keyword(s):  
Histidine Decarboxylase ◽  
Brain Histamine ◽  
Knock Out ◽  
Knock Out Mice

scholarly journals BACE1 partial deletion induces synaptic plasticity deficit in adult mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sylvia Lombardo ◽  
Martina Chiacchiaretta ◽  
Andrew Tarr ◽  
WonHee Kim ◽  
Tingyi Cao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Axonal Guidance ◽  
Knock Out ◽  
App Processing ◽  
Aged Mice ◽  
Adult Mice ◽  
Term Potentiation ◽  
Partial Depletion

AbstractBACE1 is the first enzyme involved in APP processing, thus it is a strong therapeutic target candidate for Alzheimer’s disease. The observation of deleterious phenotypes in BACE1 Knock-out (KO) mouse models (germline and conditional) raised some concerns on the safety and tolerability of BACE1 inhibition. Here, we have employed a tamoxifen inducible BACE1 conditional Knock-out (cKO) mouse model to achieve a controlled partial depletion of BACE1 in adult mice. Biochemical and behavioural characterization was performed at two time points: 4–5 months (young mice) and 12–13 months (aged mice). A ~50% to ~70% BACE1 protein reduction in hippocampus and cortex, respectively, induced a significant reduction of BACE1 substrates processing and decrease of Aβx-40 levels at both ages. Hippocampal axonal guidance and peripheral nerve myelination were not affected. Aged mice displayed a CA1 long-term potentiation (LTP) deficit that was not associated with memory impairment. Our findings indicate that numerous phenotypes observed in germline BACE1 KO reflect a fundamental role of BACE1 during development while other phenotypes, observed in adult cKO, may be absent when partially rather than completely deleting BACE1. However, we demonstrated that partial depletion of BACE1 still induces CA1 LTP impairment, supporting a role of BACE1 in synaptic plasticity in adulthood.

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