Kang et al., 2017 demonstrated that VRK3-deficient mice exhibited hyperactivity, stereotyped behaviors, reduced social interaction, impaired context-dependent spatial memory, reduced dendritic spine number and arborization in the CA1 region of the hippocampus, and altered synaptic transmission; these phenotypes could be reversed by TrkB stimulation with 7,8-dihydroxyflavone.
Molecular Function
This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. In both human and mouse, this gene has substitutions at several residues within the ATP binding motifs that in other kinases have been shown to be required for catalysis. In vitro assays indicate the protein lacks phosphorylation activity. The protein, however, likely retains its substrate binding capability. This gene is widely expressed in human tissues and its protein localizes to the nucleus. Inactive kinase that suppresses ERK activity by promoting phosphatase activity of DUSP3 which specifically dephosphorylates and inactivates ERK in the nucleus.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation.
Rescue Type:
RESCUE-Pharmaceutical
Rescue Paradigm:
Acute effect of 7,8-DHF, mice was measured at 24 h after three consecutive treatments with 7,8-DHF administered once a day. DHF was diluted in 17% DMSO to a final concentration of 10 mg/kg, and administered by intraperitoneal injection at a volume of 0.01 ml/g. For transient treatment, 7,8-DHF was administered to 12-wk-old mice once daily for three consecutive days, and mice were subjected to behavioral tests 1 and 7 d after treatment.
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.
Description: 7,8-dhf treatment markedly recovered the impaired social interaction of mutant mice compared with dmso treatment but the effect was diminished 7 d after treatment.
Exp Paradigm: NA
Description: Mutants show reductions in spine density in the ca1 and dentate gyrus regions with reductions in spine density in the ca1 more prominent on basal dendrites than apical dendrites. Exp Paradigm: NA
Description: Mutants show decrease in the ratio of ampa receptormediated currents measured at 40 and 70 mv holding potentials (also known as rectification), compared to controls, indicating a decreased proportion of ca ion-permeable ampa receptor in mutants. Exp Paradigm: NA
Description: Mutant and control mice had no preference for the right or left chambers during the habituation period of the three-chamber test. mutant mice did not show any preference for exploring a novel mouse-containing cage over a novel empty cage in a three-chamber test, compared to controls. Exp Paradigm: NA
Description: Mutant mice show reduced shredding of nest building materials compared to controls. Exp Paradigm: Nesting was scored on a scale of 0 to 3 based on the extent to which the nesting material was converted into fine pieces.
Description: Mutants mice had impaired spatial working memory compared with wt mice as indicated by increase in number of errors during the first 4 trial sessions on the barne's circular maze. Exp Paradigm: NA
Description: Mutants mice had impaired spatial reference memory compared with wt mice as indicated by the decrease in the number of correct pokes during days 5 and 12 after training and the reduction in time spent at the target during probe trial when the escape hatch was removed. Exp Paradigm: NA
Description: Mutant mice exhibited a reduced ability to discriminate between familiar and novel objects at 24 h after training, compared to controls. Exp Paradigm: NA
Cued or contextual fear conditioning: passive avoidance1
Increased
Description: Mutant mice show decrease in step-through latency compared to controls, after experiencing electric shock in a dark room. untrained mutant mice show no change in step-through latency compared to controls. Exp Paradigm: NA
Description: Mutants show increase in camkiialpha and erk phosphorylation, compared to controls. mutants show increase in phosphorylated-erk/erk ratio compared to controls. Exp Paradigm: NA
Description: Mutants show reduced levels of psd-95 and phosphorylated trkb in the synaptosomal fractions compared to controls. mutants show a slight reduction in glua1 in the synaptosomal fraction compared to controls. Exp Paradigm: NA
