Target Subcellular units | Knockout Strategies | Rhythmic phenotype | Behavioural phenotype | Other phenotypes | References | |||
---|---|---|---|---|---|---|---|---|
Global | Conventional knockout | Â | / | Â | / | + | 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 | Â | / | + | Expression of pro-inflammatory cytokines, antioxidative and anti-inflammatory factors | [143] |
Global | Conventional knockout | Â | / | + | 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 | Â | / | + | Working memory | Â | / | [130] |
 |  |  |  | + | Hippocampal-dependent memory |  |  |  |
Global | Conventional knockout | Â | / | + | 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) | Â | + | Rhythmic expression of clock genes in cortex | Â | Â | + | Expression of Nqo1 and Aldh2 (related to oxidative stress regulation) in cortexs | Â |
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 | Â | / | Â | / | [128] |
 |  × Bmal1 f/f |  |  |  |  |  |  |  |
SCN | Neuromedin s Cre | + | Behaviour rhythm | Â | / | Â | / | [129] |
 |  × Bmal1 f/f |  |  |  |  |  |  |  |
Excitatory neurons | CaMKII-Cre | Â | / | + | Hippocampal-dependent memory | Â | / | [130] |
in forebrain |  × Bmal1 f/f |  |  |  |  |  |  |  |
Excitatory neurons | CaMKII-Cre | + | Behaviour rhythm | + | Learning and memory | Â | / | [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 | Â | / | Â | / | [132] |
and SCN |  × Bmal1 f/f | + | Rhythmic expression of clock gene |  |  |  |  |  |
GABAergic | Vgat-Cre | + | Behaviour rhythm | Â | / | Â | / | [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 | Â | / | + | 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 | Â | / | Â | / | [70] |
Astrocytes | Aldh1L1-Cre ERT2 | Â | / | Â | / | + | Astrogliosis | [119] |
 |  × Bmal1 f/f |  |  |  |  | + | Expression of Chi3l1 and Mmp14 |  |
 |  |  |  |  |  |  | (Alzheimer’s related genes) |  |
Astrocytes in the AD model | Aldh1l1-CreERT2 | Â | / | Â | / | + | 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 | Â | / | Â | / | + | Astrogliosis | [119] |
(slow plaque formation) |  × Bmal1 f/f |  |  |  |  | − | Aβ plaque deposition |  |
 |  × APP NL−G−F/wt |  |  |  |  | − | Dystrophic neuropil |  |
Astrocytes in NAc | AAV8-GFAP-Cre | Â | / | + | 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 | Â | / | + | 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 | Â | / | Â | / | [140] |
 |  × Bmal1 f/f | + | Rhythmic expression of clock gene in SCN |  |  |  |  |  |
PV cell | PV-Cre ER | Â | / | + | 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 | Â | / | + | Seizures induced by pilocarpine administration | Â | / | [136] |
CRH neurons in PVN | CRH-Cre | + | Rhythmic of calcium activity in CRH neurons of PVN | Â | / | Â | / | [144] |
 |  × Bmal1 f/f |  |  |  |  |  |  |  |
 |  | + | Corticosterone release rhythm |  |  |  |  |  |
CRH neurons | CRH-Cre | − | Behaviour rhythm |  | / |  | / | [137] |
 |  × Bmal1 f/f | − | EEG and EMG |  |  |  |  |  |