Increased glyoxalase-1 levels in Fkbp5 knock-out mice caused by Glo1 gene duplication

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder, that is raising at a concerning rate. However, underlying mechanisms are still to be discovered. Obsessions and compulsions are the most debilitating aspect of these disorders (OCD), and they are the treatment priority for patients. SAPAP3 knock out mice present a reliable mouse model for repetitive compulsive behavior and are mechanistically closely related to the ASD mouse model Shank3 on a molecular level and AMPA receptor net effect. The phenotype of SAPAP3 knock out mice is obsessive grooming that leads to self-inflicted lesions by 4 months of age. Recent studies have accumulated evidence, that epigenetic mechanisms are important effectors in psychiatric conditions such as ASD and OCD. Methylation is the most studied mechanism, that recently lead to drug developments for more precise cancer treatments. We injected SAPAP3 mice with an epigenetic demethylation drug RG108 during pregnancy and delayed the onset of the phenotype in the offspring by 4 months. This result gives us clues about possible mechanism involved in OCD and ASD. Additionally, it shows that modulation of methylation mechanisms during development might be explored as a preventative treatment in the cases of high inherited risk of certain mental health conditions.

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Faculty Opinions recommendation of Dramatically decreased cocaine self-administration in dopamine but not serotonin transporter knock-out mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1158187.618307 ◽

2009 ◽

Author(s):

Jean-Antoine Girault

Keyword(s):

Serotonin Transporter ◽

Self Administration ◽

Knock Out ◽

Knock Out Mice

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Faculty Opinions recommendation of Development of single retinofugal axon arbors in normal and β2 knock-out mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.9777956.10475054 ◽

2011 ◽

Author(s):

Uwe Drescher

Keyword(s):

Knock Out ◽

Knock Out Mice

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A role of the subdiaphragmatic vagus nerve in depression-like phenotypes in mice after fecal microbiota transplantation from Chrna7 knock-out mice with depression-like phenotypes

Brain Behavior and Immunity ◽

10.1016/j.bbi.2020.12.032 ◽

2021 ◽

Author(s):

Yaoyu Pu ◽

Yunfei Tan ◽

Youge Qu ◽

Lijia Chang ◽

Siming Wang ◽

...

Keyword(s):

Vagus Nerve ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Knock Out ◽

Knock Out Mice

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

Nature Communications ◽

10.1038/s41467-021-22301-1 ◽

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.

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