Extension of the Lifespan of a Mouse Model of Rett Syndrome by Intracerebroventricular Delivery of MECP2

DearEditors,Rett Syndrome(RTT)is a severe neurodevelopmental disorder characterized by neural dysfunctions and a reduced lifespan,mainly in female patients,involving loss-of-function mutations in the methyl-CpG binding protein 2(MECP2)gene[1-4].

Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques

Dear Editor,Coronavirus disease 2019(COVID-19)is a highly infectious respiratory disease that continues to pose a serious global public health emergency.The disease shows a high infection rate,long incubation period,and rapidly emerging variants,which have led to its rapid spread worldwide(Krammer 2020).Many vaccines have been developed for the control of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for COVID-19,including vaccines based on messenger RNA(mRNA)(Polack et al.2020),viral vectors(Zhu et al.2020),recombinant proteins(Yang et al.2020),and inactivated SARS-CoV-2(Zhang et al.2021).

Loss of CREST leads to neuroinflammatory responses and ALS-like motor defects in mice

Background:Amyotrophic lateral sclerosis(ALS)is a late onset neurodegenerative disease with fast progression.ALS has heavy genetic components in which a series of genetic mutations have been identified.In 2013,Mutations of the CREST gene(also known as SS18L1),which functions as a calcium-regulated transcriptional activator,were found in sporadic ALS patients.However,the pathogenic causality and mechanisms of ALS-associated mutations of CREST remain to be determined.Methods:In this study,we constructed CREST knockout and Q394X knock-in mice with CRISPR/Cas9 system.Using biochemical and imaging tools,we illustrated core pathological phenotypes in CREST mutant mice and claimed the possible pathogenic mechanisms.Furthermore,we also observed locomotion defects in CREST mutant mice with behavioural tests.Results:We demonstrate that ALS-related CREST-Q388X mutation exhibits loss-of-function effects.Importantly,the microglial activation was prevalent in CREST haploinsufficiency mice and Q394X mice mimicking the human CREST Q388X mutation.Furthermore,we showed that both CREST haploinsufficiency and Q394X mice displayed deficits in motor coordination.Finally,we identified the critical role of CREST-BRG1 complex in repressing the expression of immune-related cytokines including Ccl2 and Cxcl10 in neurons,via histone deacetylation,providing the molecular mechanisms underlying inflammatory responses within mice lack of CREST.Conclusion:Our findings indicate that elevated inflammatory responses in a subset of ALS may be caused by neuron-derived factors,suggesting potential therapeutic methods through inflammation pathways.

Identification of CHMP4C as a new risk gene for inherited dilated cardiomyopathy

Dilated cardiomyopathy(DCM) is a primary myocardial disease of unknown cause that is characterized by ventricular enlargement and ventricular systolic dysfunction(Reichart et al., 2019). DCM exhibits obvious heterogeneity, and its outcomes extend from arrhythmia to heart failure. Early arrhythmia is a common condition that may progressively become aggravated, and death can occur at any stage of the disease. The most serious complications are heart failure and sudden death(Mc Nally et al., 2013).