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Relevance to Autism

Atg7-conditional knockout mice, which were specifically autophagy-deficient in forebrain excitatory neurons, exhibited ASD-like behaviors and dendritic spine pruning defects (Tang et al., 2014).

Molecular Function

This gene encodes a E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy; this enzyme also plays a key role in the maintenance of axonal homeostasis and the prevention of axonal degeneration.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits.
Support
Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
ASD
Support
Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.
DD, ID, epilepsy/seizures
Microcephaly
Support
GABARAPs dysfunction by autophagy deficiency in adolescent brain impairs GABAA receptor trafficking and social behavior.
Recent Recommendation
Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN623R001a 
 missense_variant 
 c.1418T>C 
 p.Leu473Pro 
  
 Both parents 
 Unknown 
 GEN623R002 
 stop_gained 
 c.1894C>T 
 p.Arg632Ter 
 Familial 
 Paternal 
 Multiplex 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
3
Deletion-Duplication
 19
 
3
Duplication
 1
 
3
Deletion
 1
 
3
Deletion
 1
 
3
Duplication
 1
 
3
Duplication
 1
 
3
Duplication
 1
 
3
Duplication
 2
 
3
Deletion
 2
 

Model Summary

Atg7 null mice die within one day of birth. Loss of Atg7 specifically in hematopoietic stem cells leads to severe myeloproliferation, and death of mice within weeks. Loss of Atg7 in the liver leads to liver adenomas.

References

Type
Title
Author, Year
Primary
Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits.
Additional
Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits.

M_ATG7_1_CKO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Conditional deletion of exons 14-17 of the Atg7 using CamkIIcre mice in excitatory neurons of the forebrain
Allele Type: Targeted (conditional ready))
Strain of Origin: (C57BL/6NCrlj x CBA/JNCrlj)F
Genetic Background: C57BL/6
ES Cell Line: TT2
Mutant ES Cell Line:
Model Source: JAX

M_ATG7_1_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic architecture: spine density1
Increased
Description: At P29-30, Atg7 CN KO mice had significantly increased spines in layer V pyramidal neurons of the auditory and sec. somatosensory cortex , indicating a deficit in spinal pruning that reduces the number of spines by this age in wild type littermate controls
 Histology
 4 weeks
Macroautophagy: neuronal1
Decreased
Description: Macroautophagy is decreased between P21-30 in Atg7 CN KO mice as determined by decrease in levels of Atg5-12 and LC3-II protein
Exp Paradigm: Western blot: Atg5-12 and LC3-II from mouse brain homogenate
 Western blot
 4 weeks
Macroautophagy: neuronal1
Decreased
Description: Macroautophagy is decreased between P21-30 in Atg7 CN KO mice as determined by decrease in levels of Atg5-12 and LC3-II protein
Exp Paradigm: Immunohistochemistry
 Immunohistochemistry
 4 weeks
Social interaction1
Decreased
Description: Atg7 CN KO mice spend less time sniffing the social stimulus mouse than control littermates, in the reciprocal social interaction test
 Reciprocal social interaction test
 4 weeks
Social approach1
Decreased
Description: Atg7 CN KO mice spend less time with social target than control littermates, in the three chamber test
 Three-chamber social approach test
 4 weeks
Social memory1
Decreased
Description: Atg7 CN KO mice do not spend more time with a new social target (new mouse) compared to a familiar mouse in the three chamber test, unlike control littermates
 Three-chamber social approach test
 4 weeks
Protein expression level evidence1
Increased
Description: Increased p 62 levels were seen between P21-P30 in Atg7 CN KO mice, indicating an accumulation of the protein which is an indication of deficit in autophagy
 Western blot
 4 weeks
Anxiety1
 No change
 Open field test
 Unreported
Astrogliosis1
 No change
 Immunohistochemistry
 Unreported
General locomotor activity: ambulatory activity1
 No change
 Open field test
 Unreported
Dendritic architecture: dendritic tree complexity1
 No change
 Histology
 P19-P20, P20-P30
Dendritic architecture: spine density1
 No change
 Histology
 P19-P20
Self grooming: perseveration1
 No change
 Grooming behavior assessments
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Learning & memory, Maternal behavior, Physiological parameters, Seizure, Sensory

 

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