Elevated levels of ATP8A1 protein was observed in the hippocampus and temporal lobe of juvenile autistic subjects compared to controls in Kerr et al., 2016. In the same report, intra-hippocampal injection of ATP8A1-expressing lentivirus in mice resulted in fewer and weaker excitatory synapses in the CA1 region, as well as autistic-like social behavior in the three-chambered social test.
Molecular Function
The protein encoded by the ATP8A1 gene is a catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Aberrant hippocampal Atp8a1 levels are associated with altered synaptic strength, electrical activity, and autistic-like behavior.
Both gain and loss of function of Atp8a1 in early development lead to disruptions in brain connectivity but only Atp8a1 gain of function is associated with aberrant social behavior and is therefore a model for autism research; Atp8a1 is elevated in the hippocampus and temporal cortex of juvenile autistic subjects;.
References
Type
Title
Author, Year
Primary
Aberrant hippocampal Atp8a1 levels are associated with altered synaptic strength, electrical activity, and autistic-like behavior.
Model Type:
Genetic
Model Genotype:
Unreported
Mutation:
Atp8a1 heterozygous null mice were crossed to generate homozygous null mice;.
Allele Type: Targeted
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: Unreported
Mutant ES Cell Line: Unreported
Model Source: C57BL/6 mice from Taconic farm and Atp8a1 heterozygous null mice from Jackson Laboratories;
Model Type:
Genetic
Model Genotype:
Unreported
Mutation:
C57BL/6 mice were injected intra-hippocampally with recombinant lentivirus expressing GFP tagged Atp8a1 (pLVX-Atp8a1-GFP) at P6 after anesthetization with ip injection of ketamine (60mg/kg) and xylazine (6mg/kg) ;.
Allele Type: Transgenic (marker)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: Unreported
Mutant ES Cell Line: Unreported
Model Source: C57BL/6 mice from Taconic farm and Atp8a1 heterozygous null mice from Jackson Laboratories;
Description: Transmission tem analyses reveal fewer and weaker excitatory synapses and multiple active zones in the hippocampal ca1 region of the atp8a1 null mice compared to the control-injected mice; atp8a1null mice also have less excitatory synapses containing multiple active than the wt; atp8a1 mice showed significantly less mature excitatory synapses with multiple active zones;
Exp Paradigm: Males only, 4 months (controls)
Description: Paired-pulse assay indicates significant inhibition at 20 ms inter-stimulus interval in atp8a1 homozygous null mice compared to wild-type controls; at 20 ms, the strength of the second response was equal to the strength of the first in the wt mice, whereas the strength of the second response was 80% of the first in the atp8a1 homozygous null mice, indicating significant inhibition; comparison of first response in the atp8a1 over-expressing and null mice shows a reduced first response in the atp8a1 over-expressing mice but not in the atp8a1 null mice;
Exp Paradigm: Paired-pulse stimulation of the schaffer collateral pathway of the mouse hippocampus was performed; field epsp was recorded from the dendritic region of ca1; amplitude of the second response was divided by the amplitude of the first in order to obtain a paired-pulse ratio;
Description: Transmission tem analyses reveal fewer and weaker excitatory synapses and multiple active zones in the hippocampal ca1 region of the atp8a1 over-expressing mice compared to the control-injected mice;
Exp Paradigm: Males only,
Description: At 20 ms time intervals, the strength of the second response was equal to the strength of the first for the control-injected mice, in contrast, strength of the second response was 85% of the first in the atp8a1+ mice indicating significant inhibition;
Exp Paradigm: Paired-pulse stimulation of the schaffer collateral pathway of the mouse hippocampus was performed; field epsp was recorded from the dendritic region of ca1; amplitude of the second response was divided by the amplitude of the first in order to obtain a paired-pulse ratio;
Description: In contrast to mice over-expressing atp8a1 in the hippocampus, control-injected mice spent a significantly longer period of time exploring the target mouse than the empty cage;
Exp Paradigm: All mice tested were males; 4 months (controls)
Description: Live imaging confirmed successful lentiviral transduction of atp8a1-gfp in mouse hippocampi; gfp fluorescence was observed in the hippocampi of mice that were injected with the control plvx-gfp virus; images from non-injected mice showed only background fluorescence;
Exp Paradigm: Fluorescence microscopy;
