To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. Exploratory analyses examining specific sub-groups of the AGP discovery cohort and a smaller replication cohort from AGRE identified two SNPs within the ST8SIA2 gene with strong association signals for the verbal sub-group (Anney et al., 2010).
Molecular Function
The protein encoded by this gene is a type II membrane protein that is thought to catalyze the transfer of sialic acid from CMP-sialic acid to N-linked oligosaccharides and glycoproteins. The encoded protein may be found in the Golgi apparatus and may be involved in the production of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). This protein is a member of glycosyltransferase family 29.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
A genome-wide scan for common alleles affecting risk for autism.
Rescue Type:
RESCUE-Pharmaceutical
Rescue Paradigm:
Mice bearing the targeted deletion of exon 4 were cerebrally infused with 40 microgram/microliter D-cycloserine through intra-cerebro-ventricular infusions (i.c.v).
Treatment does not improve measured phenotype (was expected to do so)
Ameliorated
Treatment provides partial correction or improvement of measured phenotype
No adverse effect
Treatment does not affect the parameter adversely
Sustained effect
Treatment has long term effect of restoration or amelioration, tested AFTER stopping administration (not applied for continuing long-term treatment) . Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
No sustained effect
Treatment has no long term of restoration or amelioration detectable, after stopping administration. Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
Miniature post synaptic current amplitude: excitatory1
Side effect
Description: Acute application of dcs reversibly increased nmdar currents in mutants and wildtype controls.
Exp Paradigm: Acute coronal slices were used in electrophysiology
Description: Acute application of dcs restored sustained potentiation in mutants to wildtype controls levels.
Exp Paradigm: Acute coronal slices were used in electrophysiology
Description: Cerebroventricular dcs infusion normalized increased aggression in mutants.
Exp Paradigm: Assay was performed 2 weeks after surgery for dcs infusion and 20 mins after actual dcs i.c.v infusion.
Description: St8sia2 null mice have disorganized patterns of parallel fibers in the reticular thalamic nucleus with a significant decrease on levels of vglut2, compared to littermate controls. level of vglut1 was similar to littermate controls Exp Paradigm: Lysates from frontal cortex were used to determine levels of vglut1 and vglut2- western blot
Description: Mutants show more thin and less mushroom like spines than control mice. Exp Paradigm: Syn-gfp-wpre lentivirus were infused in the amygdala to visualize synaptic morphology.
Description: Abnormal brain cytoarchitecture: mistargeting of hippocampal infrapyramidal mossy fibers and mossy fibers along ventral side of granule cell layer association with ectopic synapses Exp Paradigm: Timm's staining on hippocampal slices
Description: Mutants show smaller excitatory synapses compared with controls. mutants show reduced expression of glun2b along with weakened glutamatergic synapses. Exp Paradigm: NA
Description: St8sia2 null mice show an enlargement of lateral ventricles relative to wildtype littermates. ( brain morphology was highly variable in st8sia2 null mice) Exp Paradigm: NA
Description: St8sia2 null mice show a marked decrease in the volume of the thalamus and internal capsule compared to wild type littermates. (brain morphology was highly variable in st8sia2 null mice) Exp Paradigm: NA
Description: St8sia2 null mice have disorganized patterns of parallel fibers in the reticular thalamic nucleus with a significant decrease on levels of vglut2, compared to littermate controls. level of vglut1 was similar to littermate controls Exp Paradigm: Lysates from frontal cortex were used to determine levels of vglut1 and vglut2-immunohistochemistry
Description: Mutants subjected to resident-intruder test show decreased phospho-erk activation in neurons of the medial. basal and central but not lateral amygdala compared with controls, indicating decrease in neuronal activation. mutants subjected to fear conditioni Exp Paradigm: NA
Description: Mutants show a decrease in effectivity of tetanic stimulation on the level of synaptic ltp compared with controls that showed robust ltp of epsps upon pairing tetanic stimulation with postsynaptic depolarization which was prevented by nmdar blockade with Exp Paradigm: NA
Description: Mutants show reduction in nmdar-mediated output at cortical synapses compared with controls, as measured by input-output curves of glutamatergic currents. Exp Paradigm: NA
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission
Decreased
Description: Mutants show increase of ampa/nmda ratio at the cortical input compared with controls. Exp Paradigm: Synaptic responses were evoked at cortical inputs, through stimulation of the external
Description: Mutants show decreased sensitivity of nmdar currents to the glun2b blocker cp-101606, compared with controls, indicating a reduced contribution of glun2b to the synaptic population of nmdars. Exp Paradigm: NA
Description: St8sia2 null mice showed no preference for the sucrose solution, whereas littermate controls shows a clear preference for it. however, in a taste aversion test, st8si2 null mice chose to drink tap water over 0.1m hcl, indicating that taste processing in general is not affected in this group Exp Paradigm: Tested the preference for sucrose solution to water and for tap water to 0.1 m hcl.
Description: Mutants show decreased latency to attack male intruder, increased number of bites in vulnerable parts of the male intruder and increased numbers of attacks on the male intruder while the intruder was submissive, compared with controls. Exp Paradigm: NA
Description: Mutants show decreased anxiety levels as they spend more time in the anxiogenic center of the open field compared with controls. Exp Paradigm: NA
Description: St8si2 null mice improved their performance in the eight arm maze over training, similar to littermate controls. however, st8sia2 null mice made significantly more revisiting errors compared to controls. latencies to obtain food pellets was the same between genotypes Exp Paradigm: Eight arm radial maze
Description: Both short and long-term recognition memory is impaired in the st8sia2 null mice. Exp Paradigm: Short and long term memory analyzed. habituation to two similar objects on day 1. introduction to a new object, replaced by one of the old objects, 2 hrs and 24 hrs later.
Description: While both groups of mice performed above chance, the performance of st8si2 null mice was significantly worse than that of littermate controls during the whole period of testing Exp Paradigm: Delayed alternation with food reward, food deprivation to 85% of weight.
Cued or contextual fear conditioning: memory of cue3
Decreased
Description: Mutants show no change in freezing response during the training phase but show decreased freezing when the acoustic conditional stimulus was presented in a new context during tone test, compared with controls. Exp Paradigm: NA
Description: Mutants show decreased transcript levels of the glutamatergic cell adhesion molecule, ncam, transcript compared with controls. Exp Paradigm: NA
Description: Mutants show reduction in st8sia2 transcript in the amygdala compared to controls. wildtype controls show peak expression of st8sia2 at p5 and decay from p15 onwards. Exp Paradigm: NA
