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Table 1 Recent advances in abnormal Bmal1 expression and phenotype research through gene editing

From: Neural function of Bmal1: an overview

Target Subcellular units

Knockout Strategies

Rhythmic phenotype

Behavioural phenotype

Other phenotypes

References

Global

Conventional knockout

 

/

 

/

+

Astrogliosis

[120]

      

+

Synaptic terminals

 
      

+

fcOIS

 

Global

Conventional knockout

+

Rhythmic expression of clock genes in brain

+

Novelty-induced hyperactivity

+

Reactive oxygen species homeostasis

[126]

Global

Conventional knockout

+

Expression of clock gene in microglia

 

/

+

Expression of pro-inflammatory cytokines, antioxidative and anti-inflammatory factors

[143]

Global

Conventional knockout

 

/

+

Social behaviours

+

Excitatory synaptic transmission

[10]

    

+

Stereotyped and repetitive behaviors

+

Spontaneous firing

 
    

+

Motor coordination

+

mTOR signaling

 
    

+

Anxiety-like behavior

+

Density and morphology of dendritic

 
    

−

Depressive-like behavior

 

Spines in Purkinje cell

 

Global

Conventional Knockout

 

/

+

Working memory

 

/

[130]

    

+

Hippocampal-dependent memory

   

Global

Conventional knockout

 

/

+

Vocalizations during maternal separation

+

mTOR signalling

[112]

 

(heterozygote)

  

+

Social behaviours

   
    

+

Tereotyped and repetitive behaviors

   
    

+

Anxiety-like behavior

   
    

+

Motor coordination

   
    

−

Novel object recognition memory

   

Most neurons, astrocytes

Nestin Cre

−

Behaviour rhythm

−

Response to novel environments

+

Astrogliosis

[120]

and oligodendrocytes

 × Bmal1 f/f

    

+

Microglia activation

 

(except microglia)

 

+

Rhythmic expression of clock genes in cortex

  

+

Expression of Nqo1 and Aldh2 (related to oxidative stress regulation) in cortexs

 

Whole Brain

siRNA ICV injection

−

Behaviour rhythm

+

Depressive-like behavior

−

Orexin A, CRH, GABA levels

[8]

  

+

PSG: sleep/wake changes

     

SCN

Short hairpin RNA

+

Behaviour rhythm

+

Learned helplessness paradigm

−

Corticosterone levels

[127]

 

Injection into SCN

+

Rhythmic expression of clock gene

+

Depressive-like behavior

   
    

+

Anxiety-like Behavior

   
    

+

Weight

   

Most cells in SCN

Synaptotagmin10 Cre

+

Behaviour rhythm

 

/

 

/

[128]

 

 × Bmal1 f/f

       

SCN

Neuromedin s Cre

+

Behaviour rhythm

 

/

 

/

[129]

 

 × Bmal1 f/f

       

Excitatory neurons

CaMKII-Cre

 

/

+

Hippocampal-dependent memory

 

/

[130]

in forebrain

 × Bmal1 f/f

       

Excitatory neurons

CaMKII-Cre

+

Behaviour rhythm

+

Learning and memory

 

/

[131]

in forebrain

 × Bmal1 f/f

  

−

Depressive-like behavior

   
    

−

Anxiety-like Behavior

   

Forebrain

Inhibition of BMAL1 function (dnBMAL1)

−

Behaviour rhythm

+

Memory retrieval

+

DA-cAMP signalling

[9]

 

 × CaMKII-tTA

  

−

Anxiety-like Behavior

+

Phosphorylation of GluA1 S845

 

Neurons in forebrain

Camk2a:: iCre BAC

+

Behaviour rhythm

 

/

 

/

[132]

and SCN

 × Bmal1 f/f

+

Rhythmic expression of clock gene

     

GABAergic

Vgat-Cre

+

Behaviour rhythm

 

/

 

/

[133]

and glycinergic neurons

 × Bmal1 f/f

       

Astrocytes

Glast -CreER

+

Behaviour rhythm

+

Short- and long-term memory

+

Expression of VIP in the SCN

[48]

 

 × Bmal1 f/f

+

Rhythmic expression of clock gene in the cortex and hippocampus

  

+

Expression of GABA transporters in Astrocytes

 
      

+

GABA levels

 

Astrocytes

Glast -CreER

+

Rhythmic expression of clock gene in hypothalamic

 

/

+

Energy balance

[138]

 

 × Bmal1 f/f

    

+

Glucose homeostasis

 
      

+

Lifespan

 
      

+

Weight

 
      

+

Astrogliosis in the cortex and hippocampus

 
      

+

Glu/GABA levels

 

Astrocytes in the SCN

Bmal1 guide RNAs injected into the SCN of Aldh1L1-Cre mice

+

Behaviour rhythm

 

/

 

/

[70]

Astrocytes

Aldh1L1-Cre ERT2

 

/

 

/

+

Astrogliosis

[119]

 

 × Bmal1 f/f

    

+

Expression of Chi3l1 and Mmp14

 
       

(Alzheimer’s related genes)

 

Astrocytes in the AD model

Aldh1l1-CreERT2

 

/

 

/

+

Astrogliosis

[119]

(rapid plaque formation)

 × Bmal1 f/f

    

−

Fibrillar amyloid plaques

 
 

 × APP/PS1-21

    

−

Dystrophic neuropil

 
      

−

Microglia activation

 

Astrocytes in the AD model

Aldh1l1-Cre ERT2

 

/

 

/

+

Astrogliosis

[119]

(slow plaque formation)

 × Bmal1 f/f

    

−

Aβ plaque deposition

 
 

 × APP NL−G−F/wt

    

−

Dystrophic neuropil

 

Astrocytes in NAc

AAV8-GFAP-Cre

 

/

+

Motor response to novelty

+

Ratio of AMPA/NMDA EPSC in MSNs

[139]

 

injected into the NAc region of the Bmal1 f/f mice

  

+

Anxiety-like Behavior

+

Expression of glutamate receptors, Gclc, Pgc1α, Ldha, Mct1 and Mct2 (associated with glutathione production, mitochondrial function and lactate synthesis/metabolism)

 
      

+

Concentrations of glutathione and lactate

 

Microglia

Cx3cr1 Cre

 

/

+

Long-term memory

+

Microglial phagocytosis

[141]

 

 × Bmal1 f/f

  

+

Spatial learning and memory

+

POMC immunoreactive neurons

 
      

+

Food intake

 
      

+

Mature dendritic spines

 

Purkinje cells

L7-Cre

−

Behaviour rhythm

+

Social behaviours

+

Excitatory and inhibitory synaptic transmission

[10]

 

 × Bmal1 f/f

  

+

Stereotyped and repetitive behaviors

+

Spontaneous firing

 
    

+

Motor coordination

+

mTOR signalling

 
      

+

Purkinje cell dendrites

 

AVP neurons

AVP-Cre

+

Behaviour rhythm

 

/

 

/

[140]

 

 × Bmal1 f/f

+

Rhythmic expression of clock gene in SCN

     

PV cell

PV-Cre ER

 

/

+

Visual acuity

+

PV cells in the visual cortex

[69]

 

 × Bmal1 f/f

       

MSNs in the striatum

Gpr88-Cre

−

Behaviour rhythm

+

Voluntary alcohol intake

 

/

[134]

 

 × Bmal1 f/f

       

MSNs in the striatum

Gpr88-Cre

+

Rhythmic expression of clock gene in striatum

+

Anxiety-like Behavior

−

Mitochondrial respiration

[135]

 

 × Bmal1 f/f

  

−

Depressive-like behavior

   
    

+

Motor coordination

   

Neurons in the DG of hippocampus

Syn1-Cre AAV virus injected into the DG of Bmal1 f/f mice

 

/

+

Seizures induced by pilocarpine administration

 

/

[136]

CRH neurons in PVN

CRH-Cre

+

Rhythmic of calcium activity in CRH neurons of PVN

 

/

 

/

[144]

 

 × Bmal1 f/f

       
  

+

Corticosterone release rhythm

     

CRH neurons

CRH-Cre

−

Behaviour rhythm

 

/

 

/

[137]

 

 × Bmal1 f/f

−

EEG and EMG

     
  1. fcOIS: optical intrinsic signal functional connectivity imaging; PSG: polysomnographic recording; ICV: intracerebroventricular; EEG: electroencephalogram; EMG: electromyogram; mTORC1: mammalian target of rapamycin complex 1; NAc: nucleus accumbens; EPSC: excitatory postsynaptic currents; MSNs: moderately spiny neurons; POMC: pro-opiomelanocortin; AVP: arginine vasopressin; PV: parvalbumin; PVN: paraventricular nucleus; CRH: corticotropin-releasing hormone; DA: Dopamine. (+) indicates an abnormal phenotype has been observed; (−) indicates no difference was found; / indicates that the article does not contain information about the indicated topic/heading