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Relevance to Autism

Disruption of the MAPK8IP2 gene in mice results in reduced AMPA and enhanced NMDA receptor-mediated glutamatergic transmission in cerebellum and altered morphology of Purkinje cell dendritic arbors, as well as motor deficits and decreased social interaction (Giza et al., 2010).

Molecular Function

This gene encodes a scaffold protein that is thought to be involved in the regulation of the c-Jun amino-terminal kinase signaling pathway. This protein has been shown to interact with and regulate the activity of MAPK8/JNK1 and MAP2K7/MKK7 kinases.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2.

Rare

No Rare Variants Available

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
22
Duplication
 1
 
22
Duplication
 1
 
22
Deletion-Duplication
 9
 
22
Deletion
 1
 
22
Deletion-Duplication
 16
 
22
Deletion-Duplication
 21
 
22
Duplication
 24
 
22
Deletion-Duplication
 54
 

Model Summary

Mutant mice exhibit reduced AMPA and enhanced NMDA receptor-mediated glutamatergic transmission in cerebellum, altered morphology of Purkinje cell dendritic arbors, and motor and cognitive deficits suggesting an autism phenotype.

References

Type
Title
Author, Year
Primary
Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2.

M_MAPK8IP2_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Mapk8ip2 KO (null) with deletion of exons 3-8 of the gene by injecting Cre in the male pronucleus of floxed mice
Allele Type: Knockout
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_MAPK8IP2_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Decreased
Description: Decreased activity in a novel procedure room
Exp Paradigm: Open field test
 Open field test
 Unreported
Motor coordination and balance1
Decreased
Description: Decreased motor performance and learning
Exp Paradigm: Accelerating rotarod test
 Accelerating rotarod test
 5-6.5 weeks
Cerebellar foliation1
Decreased
Description: Decreased total dendritic intracellular volume; decreased thickness of molecular layers in lobules 3 and 4 of cerebella
Exp Paradigm: Biocytin-Oregon Green staining of live cells in acute cerebellar slices; measurements of midline sagittal vermis histological sections
 Histology: biocytin-oregon green staining
 3-4 weeks
Neurotransmitter release: quantal parameters1
Decreased
Description: Decreased minimal EPSC amplitude, quantal release probability, presynaptic glutamate release probabliity, quantum size, and paired-pulse depression
Exp Paradigm: Whole-cell patch-clamp recordings from single mossy fiber-granule cell synapses
 Whole-cell patch clamp
 P18-P22
Synaptic transmission1
Decreased
Description: Decreased AMPA/kainate EPSC peak current density and decay time
 
 Unreported
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Increased
Description: Increased NMDA/AMPA ratio indicated by decreased AMPA current with enhance NMDA current at mossy fiber-granule cell synapses
Exp Paradigm: Whole-cell patch-clamp recordings from granule cells in the presence of extracellular Magnesium at both -70 mV and +60 mV
 Whole-cell patch clamp
 P18-P22
Social interaction1
Decreased
Description: Decreased interaction times between pairs of both male and female mutant mice
Exp Paradigm: Social interaction test
 Reciprocal social interaction test
 5-6.5 weeks
Fear response1
 No Change
 Elevated T-maze test
 Unreported
General locomotor activity1
 No Change
 Open field test
 Unreported
Grip strength1
 No Change
 Grip strength test
 5-6.5 weeks
Motor coordination and balance1
 No Change
 Balance beam test
 5-6.5 weeks
Anatomical projections and connectivity1
 No Change
 Immunohistochemistry: fluorescence
 Unreported
Brain cytoarchitecture1
 No Change
 Electron microscopy
 Unreported
Cerebellar foliation1
 No Change
 Histology: biocytin-oregon green staining
 3-4 weeks
Synaptic neuroreceptors1
 No Change
 Western blot
 Unreported
Synaptic transmission1
 No Change
 Whole-cell patch clamp
 P18-P22
Olfaction1
 No Change
 Buried food test
 5-6.5 weeks
Vision1
 No Change
 Forepaw reaching test
 5-6.5 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Repetitive behavior, Seizure


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
CHD8 chromodomain helicase DNA binding protein 8 57680 Q9HCK8 CHIP-seq
Cotney J , et al. 2015
LRP2 Megalin; low density lipoprotein receptor-related protein 2 14725 A2ARV4 Y2H; GST
Gotthardt M , et al. 2000
MAPK8IP1 mitogen-activated protein kinase 8 interacting protein 1 9479 Q6NUQ9 IP; LC-MS/MS
Huttlin EL , et al. 2015
RAPGEF5 Rap guanine nucleotide exchange factor (GEF) 5 9771 A8MQ07 IP; LC-MS/MS
Huttlin EL , et al. 2015
TULP2 Tubby-related protein 2 7288 O00295 IP; LC-MS/MS
Huttlin EL , et al. 2015

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