EPS8 levels were found to be reduced in brains of patients affected by autism compared to controls (Menna et al., 2013); in this same report, it was demonstrated that mice lacking Eps8 display immature spines, which are unable to undergo potentiation, and shows deficits in learning, memory, and social behavior.
Molecular Function
Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Acts as a regulator of axonal filopodia formation in neurons: in the absence of neurotrophic factors, negatively regulates axonal filopodia formation via actin-capping activity. Defects in EPS8 are associated with some cancers, such as pancreatic, oral squamous cell carcinomas or pituitary cancers.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Eps8 controls dendritic spine density and synaptic plasticity through its actin-capping activity.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A neomycin resistance cassette replaced one exon and part of a second exon.
Allele Type: Targeted (knock-out)
Strain of Origin: 129P2/OlaHsd
Genetic Background: B6.129P2-Eps8tm1Ppdf
ES Cell Line: E14 (ES Cell)
Mutant ES Cell Line: Model Source:
Description: Eps8 ko mice did not display the increase in spine number, following training in object recognition, seen in wild type mice.
Exp Paradigm: Mice trained in object recognition were used in golgi cox method to look for learning dependent spinogenesis
Description: Cortical eeg recordings from eps8 ko mice reveal that they display frequent spikes of high amplitude, both the mean number and amplitude of these spikes is higher than in wild type mice
Exp Paradigm: Four screw electrodes are inserted bilaterally through skull over the cortex, and a full electrode is also placed into the nasal bone as ground- in anesthetized mice. a week is allowed for recovery. basal cerebral activity is recorded continuously for 24 hrs in free moving mice. mean number of spikes are evaluated every 24 h period.
Description: Eps8 ko mice spent the same amount of time in the compartmen containing the empty cage and the one containing the stranger mouse, unlike wild type controls which spent longer time to explore the compartment with the stranger mouse.
Exp Paradigm: The apparatus is a three chamber polycarbonate box. the animal to be tested was placed in the middle compartment and allowed to explore all three chambers for 10 min (habituation) . an unfamiliar adult dba/2j male mouse was placed in one side compartment, whereas the opposite compartment contained an empty wire cage. time spent in each chamber and number of entries in each chamber were recorded for 10 min. time spent to explore compartment containing the conspecific and that spent in the empty compartment (sociability) or containing the stranger animal (unfamiliar) and that for the familiar mouse ( social novelty test) is recorded
Description: Eps8 ko mice spent significantly less time in exploring the novel object compared to the familiar object, displaying a significant decrease in the discrimination index.
Exp Paradigm: Animals are exposed to two identical unfamiliar objects in the first familiarization session. this followed by the second session ( after a 120 min intersession) where one of the familiar objects is replaced with a novel object. time spent in exploring the novel object versus the familiar object ( over total time) is described as the discrimination index.
Description: Long term memory is reduced in eps8 ko mice as there is significant reduction of the mean value of step through latency compared to wild type controls, indicating loss of fear memory
Exp Paradigm: The apparatus consists of two compartments, one light and one dark, connected via a sliding door. in the acquisition trial, each mouse wsa placed in the light compartment and allowed to enter the dark compartment. time taken to do so was recorded. once the mouse was in the dark compartment, the sliding door was closed and an unavoidable electric shock was delivered via the paws. animal was placed back in the home cage and retention trial was carried out after 24 hrs. in the retention trial the time taken by the mouse to enter the dark compartment, being positioned in the light compartment to start with, was recorded.
Description: Eps8ko mice had statistically impaired performance compared to wild type controls in the acquisition phase of the t maze test
Exp Paradigm: Mice are habituated to a black wooden t-maze to obtain food (for 5 days). in the acquisition phase, one arm is designated as reinforce for each of 10 daily trials. each mouse is placed at the maze start and given a free choice to enter either arm. the 'criterion' is showing 80% correct choices for 3 days. in the reversal phase, the reinforcer arm is switched to the opposite arm- only mouse that met the criterion is tested in this phase.
Description: Eps8 ko mice exhibited increased number of errors and took increased number of days to reach the criterion, compared to wild type.
Exp Paradigm: The radial maze consisted of eight wooden arms, painted black.food pelletes were kept in small plastic cups mounted at the end of each arm. animals were kept at 90% of free eating body weight.working memory is scored based on the total number of errors, when an animal re enters an arm just visited. the 'criterion' was entering seven different arms in the first eight choices made by the animal. for achieving this criterion animals were trained every day with one trial a day. number of animals reaching the criterion in 5 days of training are shown in results
