HELP     Sign In
Search

Relevance to Autism

Pak2 +/- mice were found to exhibit reduced spine density, defective long-term potentiation, impaired actin polymerization, and autism-related behaviors, including increased stereotypic behavior and reduced social interactions (Wang et al., 2018); in the same report, a rare de novo nonsense variant and inherited damaging missense variants in the PAK2 gene were identified in Han Chinese ASD probands. PAK2 resides within the 1.5-Mb region on chromosome 3q29 that defines the 3q29 microdeletion syndrome (OMIM 609425) and may contribute to the phenotypes observed in affected individuals, including autism/autistic features and schizophrenia in some individuals (Willatt et al., 2015; Mulle et al., 2010; Quintero-Rivera et al., 2010).

Molecular Function

The PAK2 gene encodes a serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation, and that acts as downstream effector of the small GTPases CDC42 and RAC1.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
PAK2 Haploinsufficiency Results in Synaptic Cytoskeleton Impairment and Autism-Related Behavior.
ASD
Support
Autistic and psychiatric findings associated with the 3q29 microdeletion syndrome: case report and review.
3q29 microdeletion syndrome
Support
Microdeletions of 3q29 confer high risk for schizophrenia.
3q29 microdeletion syndrome
Support
3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome.
3q29 microdeletion syndrome

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN1037R001 
 stop_gained 
 c.1435C>T 
 p.Arg479Ter 
 De novo 
 NA 
 Simplex 
 GEN1037R002 
 missense_variant 
 c.931G>A 
 p.Asp311Asn 
 Familial 
 Paternal 
 Simplex 
 GEN1037R003 
 missense_variant 
 c.1570C>T 
 p.Arg524Cys 
 Familial 
 Maternal 
 Simplex 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
3
Duplication
 1
 
3
Duplication
 2
 
3
Duplication
 1
 
3
Duplication
 2
 
3
Duplication
 1
 
3
Duplication
 1
 
3
Deletion
 4
 
3
Duplication
 4
 
3
Deletion-Duplication
 55
 

Model Summary

Pak2 haploinsufficiency results in stereotyped behaviors, impaired social interaction, and abnormal synaptic morphology. Treatment with p-CFL restored social behaviors in Pak2 heterozygous mice.

References

Type
Title
Author, Year
Primary
PAK2 Haploinsufficiency Results in Synaptic Cytoskeleton Impairment and Autism-Related Behavior.

M_PAK2_1_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Pak2 gene was knocked out through gene trapping and a poly-A and a PGK promoter were inserted before the exon 2 of Pak2 to terminate the transcription.
Allele Type: LOF Knockin
Strain of Origin:
Genetic Background:
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_PAK2_2_KO_HT_R479X

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Mouse embryonic brains were transfected with PAK2-R479X plasmids by in utero electroporation
Allele Type: LOF Knockin
Strain of Origin:
Genetic Background:
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_PAK2_1_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synapse density1
Decreased
Description: Mutants showed a decrease in the synapse number in both cortex and hippocampus compared to controls.
 Electron microscopy
 2 months
Dendritic architecture: spine density1
Decreased
Description: Mutants showed a decrease in the densities of both basal and the apical dendrites compared to controls.
 Golgi-cox staining
 2 months
Anatomical projections and connectivity1
Decreased
Description: Mutants showed a decrease in neuronal tract-tracing using DiI signal compared to controls.
 Neuronal tracing
 8 weeks
Synaptic plasticity: hippocampal ltp1
Decreased
Description: Mutants showed a decrease in theta burst-induced LTP magnitude compared to controls.
 Theta burst stimulation (tbp)
 3 months
Stereotypy1
Increased
Description: Mutants buried more marbles compared to controls.
 Marble-burying test
 2 months
Self grooming: perseveration1
Increased
Description: Mutants spent more time grooming themselves compared to controls.
 Grooming behavior assessments
 2 months
Social withdrawal1
Increased
Description: Mutants showed showed avoidance behavior to a mouse in the social defeat box compared with controls.
 Reciprocal social interaction test
 2 months
Social memory1
Decreased
Description: Mutants showed a decrease in preference for a novel stimulus mouse as well as a decrease in preference index compared to controls.
 Three-chamber social approach test
 2 months
Social approach1
Decreased
Description: Mutants showed a decrease in preference for a social target over inanimate object as well as decreased social preference index compared to controls.
 Three-chamber social approach test
 2 months
Protein expression level evidence1
Decreased
Description: Mutants showed a decrease levels of phosphorylated LIM-domain-containing protein kinase 1 (LIMK 1) compared to controls.
 Western blot
 P4
Protein expression level evidence1
Decreased
Description: Mutants showed a decrease levels of filament (F)-actin compared to controls.
 Western blot
 2 months
Protein expression level evidence1
Decreased
Description: Mutants showed a decrease levels of phosphorylated LIM-domain-containing protein kinase 1 (LIMK 1) compared to controls.
 Western blot
 2 months
Gene expression1
Abnormal
Description: Mutants showed abnormal gene expression patterns, with 113 upregulated and 333 downregulated gene in the cortex and 72 upregulated and 378 downregulated genes in the hippocampus, compared to controls.
 Rna sequencing
 P2
Protein expression level evidence1
Decreased
Description: Mutants showed a decrease levels of p-cofilin (p-CFL) compared to controls.
 Western blot
 P4
Targeted expression1
Decreased
Description: Mutants showed decreased levels of Pak2 protein compared to controls.
 Western blot
 2 months
Protein expression level evidence1
Decreased
Description: Mutants showed a decrease levels of p-cofilin (p-CFL) compared to controls.
 Western blot
 2 months
Ultrasonic vocalization1
 No change
 Monitoring ultrasonic vocalizations
 P8
Anxiety1
 No change
 Light-dark exploration test
 2 months
Anxiety1
 No change
 Elevated plus maze test
 2 months
Cognitive flexibility1
 No change
 Morris water maze test
 2 months
Spatial learning1
 No change
 Morris water maze test
 2 months
Spatial reference memory1
 No change
 Morris water maze test
 2 months
Protein expression level evidence1
 No change
 Western blot
 2 months
Protein expression level evidence1
 No change
 Western blot
 2 months
General locomotor activity: ambulatory activity1
 No change
 Home cage behavior
 2 months
Brain size1
 No change
 Magnetic resonance imaging (mri)
 2 months
Cortical lamination1
 No change
 Histology
 2 months
Dti: fractional anisotropy or relative anisotropy in brain regions1
 No change
 Diffusion tensor imaging (dti)
 2 months
Epsp-spike relationship1
 No change
 Field potential recordings
 3 months
Presynaptic function: paired-pulse facilitation1
 No change
 Field potential recordings
 3 months
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission1
 No change
 Field potential recordings
 3 months
Sensorimotor gating1
 No change
 Prepulse inhibition
 2 months
Startle response: acoustic stimulus1
 No change
 Acoustic startle reflex test
 2 months
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Immune response, Maternal behavior, Physiological parameters, Seizure

M_PAK2_2_KO_HT_R479X

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal migration1
Decreased
Description: Mutants showed a decrease in the number of neurons in the cortical plate and an increase in the number of neurons in intermediate zone and subventricular zone, thus suggesting decreased neuronal migration in mutants.
 Immunohistochemistry
 E18.5
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

 

No Interactions Available
HELP
Copyright © 2017 MindSpec, Inc.