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Relevance to Autism

A SLC33A1/AT-1 Tg mouse model that selectively overexpresses human AT-1 in neurons exhibited cognitive deficits, autistic-like social behavior, aberrations in synaptic plasticity, an increased number of dendritic spines and branches, and widespread proteomic changes (Hullinger et al., 2016).

Molecular Function

The protein encoded by this gene is a probable acetyl-CoA transporter required for the formation of O-acetylated (Ac) gangliosides. A heterozygous missense variant in SLC33A1 was identified in a Chinese family presenting with spastic paraplegia (SPG42; OMIM 612539), whereas biallelic variants in SLC33A1 are associated with congenital cataracts, hearing loss, and neurodegeneration (CCHLND; OMIM 614482).

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References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Increased expression of AT-1/SLC33A1 causes an autistic-like phenotype in mice by affecting dendritic branching and spine formation.
ASD
Support
Identification and functional analysis of a SLC33A1: c.339T>G (p.Ser113Arg) variant in the original SPG42 family.
Support
Mutations in SLC33A1 cause a lethal autosomal-recessive disorder with congenital cataracts, hearing loss, and low serum copper and ceruloplasmin.
Support
A missense mutation in SLC33A1, which encodes the acetyl-CoA transporter, causes autosomal-dominant spastic paraplegia (SPG42).
No Rare Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
3
Duplication
 1
 
3
Duplication
 1
 
3
Duplication
 3
 

Model Summary

Chromosomal duplications affecting the 3q25.31 locus harboring AT-1/ SLC33A1 have been associated with autism spectrum disorder (ASD) and intellectual disability (SFARI Autism Database; http://sfari.org/; Sanders et al., 2011; Prasad et al., 2012; Krumm et al., 2013).

References

Type
Title
Author, Year
Primary
Increased expression of AT-1/SLC33A1 causes an autistic-like phenotype in mice by affecting dendritic branching and spine formation.
Model Type: Genetic
Model Genotype: Heterozyous
Mutation: Human SLC33A1 cDNA isolated and subcloned into pTRE-Tight vector was linearized and injected into the pronucleus of fertilized eggs from FVB mice; monogenic pTRE-AT-1 mice were backcrossed to WT C57BL/6 mice for five generations, and then bred to CamK2a-tTA mice; the inducible neuron-specific overexpression Tet-Off system is driven by the CamK2 promoter; the transgenic animals maintained in the absence of doxycycline (Dox) overexpressed human SLC33A1 in forebrain neurons during development and after birth.
Allele Type: Targeted (marker); Transgenic
Strain of Origin: FVB
Genetic Background: C57BL/6
ES Cell Line: FVB
Mutant ES Cell Line: FVB
Model Source: Jackson Laboratory
Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic architecture: spine density1
Increased
 Sholl analysis
 6 months
Synaptic plasticity: hippocampal ltp1
Increased
 Field potential recordings
 Adult
Synaptic plasticity: hippocampal ltd1
Decreased
 Field potential recordings
 Adult
Repetitive digging1
Decreased
 Marble-burying test
 Adult
Social memory1
Decreased
 Three-chamber social approach test
 Adult
Spatial learning1
Decreased
 Morris water maze test
 Adult
Object recognition memory1
Decreased
 Novel object recognition test
 Adult
Cued or contextual fear conditioning: context discrimination1
Decreased
 Fear conditioning test
 Adult
Spatial reference memory1
Decreased
 Morris water maze test
 Adult
Protein modification process1
Increased
 Western blot
 Adult
Marker expression1
Increased
 Mass spectrometry (ms)
 Adult
Targeted expression1
Increased
 Western blot
 Adult
Protein modification process1
Increased
 Liquid chromatography-mass spectrometry (lc-ms)
 Adult
Gene expression1
Increased
 Chromatin immunoprecipitation (chip)
 Adult
Targeted expression1
Increased
 Quantitative pcr (qrt-pcr)
 Adult
Metabolite level quantification1
Decreased
 In vitro diagnostic tests
 Adult
Proteomic profile diversity1
Increased
 Liquid chromatography-mass spectrometry (lc-ms)
 Adult
Marker expression1
Increased
 Western blot
 Adult
Anxiety1
 No change
 Open field test
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Maternal behavior, Motor phenotype, Physiological parameters, Seizure, Sensory

 

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