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.
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.
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:
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:
Description: Mutants showed a decrease in preference for a novel stimulus mouse as well as a decrease in preference index compared to controls.
Exp Paradigm: NA
Description: Mutants showed a decrease in preference for a social target over inanimate object as well as decreased social preference index compared to controls.
Exp Paradigm: NA
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.
Exp Paradigm: NA
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.
Exp Paradigm: NA
