In a genome-wide study, association was found between CNVs in the PRKN gene and autism in AGRE and ACC cohorts (European ancestry) (Glessner et al., 2009). In addition, a rare duplication in the PRKN gene has been identified in an individual with ASD (ORoak et al., 2012). As well, rare variants in the PRKN gene have been identified in individuals with autosomal recessive juvenile parkinsonism (Kitada et al., 1998).
Molecular Function
The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.
Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Targeted deletion of parkin exon 3 resulting in frameshift after amino acid 57 of parkin.
Allele Type: Targeted (Knock Out)
Strain of Origin: 129Sv/J
Genetic Background: C57BL/6
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Targeted deletion of parkin exon 3 resulting in frameshift mutation.
Allele Type: Knockout
Strain of Origin: 129S4/SvJae
Genetic Background: C57BL/6J
ES Cell Line: J1
Mutant ES Cell Line: Model Source: Jackson Laboratory
Description: Abnromal brain ultrastructure characterized by abnormal mitochondria and lipfouscin granules within dopaminergic neurons in the substantia nigra
Exp Paradigm: Electron microscopy with immunogold technique in the substantia nigra
Description: Abnormal brain ultrastructure characterized by cytoplasmic vacuoles, disruption of golgi network, endoplasmic reticulum, abnormal mitochondria - electron dense inclusion bodies, dilated and disorganzied cristae
Exp Paradigm: Electron microscopy of the substantia nigra, the striatum, and the cortex
Description: Decreased mitochondrial respiration of complex i in the presence of the uncouple cccp
Exp Paradigm: Mitochondria measurement of respiration in slices of substantia nigra in the presence of cccp
Description: Prkn knockout mice displayed an increased frequency of unsupported rearing behavior compared to wildtype mice, but no change in supported rearing behavior.
Description: Prkn knockout mice showed no difference in the average travel velocity compared to that of the wildtype mice. A slight reduction in the total distance traveled was detected, which was caused by more frequent pausing and rearing.
Description: In the frontal cortex, glutamatergic receptors GluA1, GluA2, GluA3, and GluN1 were down-regulated in brains of Prkn knockout mice. In the hippocampus, GluA2 level was increased in Prkn knockout mice. In whole frontal cortical samples, GluA1, GluA2, and GluN1, were significantly reduced in Prkn knockout mice. mRNA abundance of GluA1, GluA2, Kir2.1, and GluN1 in Prkn knockout mice were not changed compared to wildtype mice.
Description: Prkn knockout mice showed a significant reduction in spine density; the densities of mushroom and thin spines, as well as filopodia. When comparing the spine density at apical and basal dendrites of hippocampal CA1 pyramidal neurons, no significant difference in spine density was detected.
Description: Prkn knockout mice brains showed a reduction in the complexity of basal dendritic arborization and dendritic tip number relative to the wildtype mice.
Exp Paradigm: Sholl analysis
Description: In layer 5, the puncta density of the excitatory pre-synaptic marker VGlut1 in Prkn knockout mouse brains was reduced as compared to that in wildtype mouse brains. In layer 2 of the prelimbic cortex, the puncta densities of VGlut1 was decreased in Prkn knockout mice. In the hippocampal CA1 region, the puncta density of VGlut1 was not altered.
Description: Prkn knockout mice brains showed decreases in total dendritic length and the length of the longest dendritic branch; However, the average dendrite length in the Prkn knockout mice remained the same as in wildtype mice.
Description: In Prkn knockout mouse brains, the sociability test resulted in decreased c-fos positive cells in the prelimbic cortex and in layer 5 compared to wildtype mice.
Description: Prkn knockout mice displayed a higher level of grooming behavior in terms of both the number of grooming episodes and the total time of grooming compared to wildtype controls.
Description: Prkn knockout mice displayed no preference toward the novel social target by spending an equal amount of time in either of the side chambers containing familiar and novel mouse.
Description: Prkn knockout mice showed a reversed preference by spending significantly more time in the empty chamber vs. the chamber with the stranger mouse compared to wildtype mice.
Description: Prkn knockout pups showed a reduction in call number at P7-13 (tested P5-P13). The absolute call rate in Prkn knockout pups was significantly reduced at P7, P9, and P11 compared to that in the wildtype pups. At P5, Prkn knockout pups demonstrated a longer call duration and higher peak frequency, but no change in total call time.
Description: Prkn knockout mice showed comparable numbers in inner square crossings and center square crossings compared to wildtype mice. However, Prkn knockout mice spent a longer time in the inner square area and less time near the wall area.
Description: In the frontal cortex, ubiquitin signals were reduced in Prkn knockout mice. In the hippocampus, ubiquitin signals remained unchanged across wildtype and Prkn knockout mouse brains.
Description: The amount of synaptosomal GluA1, GluA2, GluN is decreased, while synaptosomal marker PSD-95 in unchanged in Prkn knockout mice compared to wildtype controls.
