Conditional stb knockout mice were found to display core autism-like traits, including deficits in social recognition and communication, increased stereotypic behavior, and impaired spatial learning and memory; furthermore, functional analysis of a de novo missense variant in the SYBU gene observed in an ASD proband demonstrated that this variant resulted in the loss of adapter capacity for binding kinesin-1 motors and failure to rescue reduced synapse formation and impaired synaptic transmission and plasticity in neurons from stb cKO mice.
Molecular Function
Syntabulin/GOLSYN is part of a kinesin motor-adaptor complex that is critical for the anterograde axonal transport of active zone components and contributes to activity-dependent presynaptic assembly during neuronal development.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Defects in syntabulin-mediated synaptic cargo transport associate with autism-like synaptic dysfunction and social behavioral traits
Mice with conditional deletion of Sybu in neurons show no change in viability or fertility, decreased body weight, decreased ability to compete for food and water during early development, decreased axonal transport, decreased synaptogenesis, decreased spine density in hippocampal pyramidal neurons especially mushroom spines, abnormal structures of synaptic active zones, decreased synaptic function, impaired synaptic plasticity. 8-10 weeks old sybu cKO mice show no change in sociability but decreased social recognition, no change in non social odor recognition, decreased communication, increased self-grooming, and impaired spatial learning and memory. Sybu cKO mice show no changes in aggression, motor coordination and balance, locomotor activity, anxiety andsensory perception. Expressing human ASD linked Sybu variant Sybu-R178Q fails to rescue reduced synapse formation and impaired synaptic transmission and plasticity in sybu cKO neurons.
References
Type
Title
Author, Year
Primary
Defects in syntabulin-mediated synaptic cargo transport associate with autism-like synaptic dysfunction and social behavioral traits
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Nestin-Cre; stbLoxP/LoxP cKO mouse, in which central and peripheral nervous system-selective inactivation of the sybu gene was achieved by deleting exons 4 and 5, leading to a frameshifting that generates a premature stop codon in exon 6 after crossing stb^LoxP/LoxP and Nestin-Cre mice.
Allele Type: Conditional knockout
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: NA
Mutant ES Cell Line: C57BL/6N Tac
Model Source: NA
Description: Decreased active zone density and reduced number of total and docked synaptic vesicles per active zone, no change in length of the active zone
Exp Paradigm: NA
Description: Decreased amplitude and downward shift of inputoutput (i/o) curves of field epsps at sc-ca1 synapses across a series of stimulation intensities
Exp Paradigm: NA
Description: Increase in time taken to learn the new location of the platform on days 9 to 12 when the hidden platform was moved to the opposite quadrant of the pool
Exp Paradigm: NA
Cued or contextual fear conditioning: memory of context1
Decreased
Description: Decrease in time spent freezing after each foot shock; decrease in time spent freezing during the first 5 min of the extinction phase, indicating an impairment in contextual fear memory retrieval
Exp Paradigm: NA
