A number of studies have focused on the genetic association of the MET gene with autism. Positive associations have been found in the Caucasian, Japanese and Italian populations as well as in AGRE family cohorts from multiple studies. Interestingly, a positive association with MET and schizophrenia has also been found, but no association was found with PDD. In addition, biochemical studies have been performed that show a reduction in MET protein levels and general disruption of MET signaling in ASD patients.
Molecular Function
The encoded protein is the hepatocyte growth factor receptor with tyrosine-kinase activity. The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
A genetic variant that disrupts MET transcription is associated with autism.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exon 16 of Met gene using Albumin-cre, in the liver
Allele Type: Conditional loss-of-function
Strain of Origin: Not Specified
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Point mutation in Met receptor impairing signal transduction through the Ras/MAP kinase pathway.
Allele Type: Targeted (Mutation)
Strain of Origin: CD1
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Charles River
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exon 16 of Met using Emx-cre in neurons and glia of neocortex, hippocampus and other brain regions
Allele Type: Conditional loss-of-function
Strain of Origin: Not Specified
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Conditional heterozygous deletion of exon 16 of Met gene using Emx1-cre, in neurons and glia of the neocortex, hippocampus and pallium, E10.5 onwards
Allele Type: Conditional loss-of-function
Strain of Origin: Not Specified
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Conditional heterozygous deletion of exon 16 of the Met gene using Nestin-cre, in neuronal, glial and other cell types in the central and peripheral nervous system
Allele Type: Conditional loss-of-function
Strain of Origin: Not Specified
Genetic Background: C57Bl/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Judson et al, 2009 [PMID: 19226509]
Model Type:
Genetic; Induced
Model Genotype:
Heterozygous
Mutation:
Heterozygous Met CKO, with loss of Met from neurons and glia, were administered early life stress by giving dams reduced amount of nesting material and placing a wire mesh on the cage floor. Wild-type mice raised in standard rearing conditions were used as controls. .
Allele Type: Conditional loss-of-function
Strain of Origin: Not Specified
Genetic Background: C57Bl/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Judson et al, 2009 [PMID: 19226509]
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Targeting vector replaced 2 kilobases (kb) of genomic DNA that included the codon for an invariant lysine essential for kinase activity.
Allele Type: Targeted (Mutation)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6/129
ES Cell Line: E14
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Targeting vector replaced 2 kilobases (kb) of genomic DNA that included the codon for an invariant lysine essential for kinase activity.
Allele Type: Targeted (Mutation)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6/129
ES Cell Line: E14
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A human cDNA fragment containing an Tyrosine to Phenylalanine (YtoF) amino acid substitution in two positions: 1349 and 1356 fused in-frame with the exon 3 of genomic clone. The mutation of both tyrosines of the protein leads to complete loss of function of Methionine tyrosine kinase.
Allele Type: Targeted (knock-in)
Strain of Origin: Not Specified
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A human cDNA fragment containing an Asparagine to Histidine amino acid substitution at position 1358 (N1358H) fused in-frame with the exon 3 of genomic clone. This generates a methionine tyrosine kinase that cannot bind Grb2, and therefore cannot activate the Ras pathway.
Allele Type: Targeted (knock-in)
Strain of Origin: Not Specified
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Description: Significantly higher apoptotic response in -vitro and in vivo to fas stimulation
Exp Paradigm: Measurement of survival and apoptosis after fas stimulation using jo-2 antibody
Description: Significant reduction in bacterial uptake indicating loss of phagocytic activity.
Exp Paradigm: Primary culture incubated with opsonized e. coli and bacterial uptake was measured using a confocal microscope.
Description: Abnormal immune system response
Exp Paradigm: Primary culture incubated with opsonized e. coli and bacterial uptake by hepatocytes was measured using a confocal microscope.
Description: Decreased healing and regeneration after injury due to ccl4 only after pretreatment with phenobarbital.
Exp Paradigm: Toxic liver injury induced by a single injection of ccl4
Description: Decreased activation of ras/map kinase pathway indicated by decreased phosphorylation of erk after treatment with bdnf
Exp Paradigm: Ras/map kinase activation
Description: Increased spine head volume in layers 5 and 2/3 and of medium spiny neuron spines with rightward shift in frequency distribution of spine classes
Exp Paradigm: 3d renderings of confocal image stacks
Description: Abnormally altered total dendritic length distal to stoma within the arbors of layer 5 and layer 2/3 pyramidal neurons; decreaed brancing complexity specific to apical dendritic compartment
Exp Paradigm: Sholl analysis of acc pyramidal dendrites
Description: Increased total dendritic length of dendritic arbors of striatal medium spiny neurons beginning appromixately 50 micrometers from cell body
Exp Paradigm: Lucifer yellow microinjection technique of striatal medium spiny neurons; increased branching and branching complexity of higher order dendrites
Description: Increased amplitude of layer2/3 excitatory input to corticostriatal neurons in upper layer 5b
Exp Paradigm: Mapping of excitatory synaptic inputs with lsps from corticostriatal neurons in afc
Description: Increased amplitude of layer2/3 excitatory input to corticostriatal neurons in upper layer 5b
Exp Paradigm: Mapping of excitatory synaptic inputs with lsps from corticostriatal neurons in afc
Description: Mutants show decrease in basal dendritic length of hippocampal ca1 neurons compared to controls.
Exp Paradigm: Ventral hippocampal ca1 pyramidal neurons that project to the bla were scored.
Dendritic architecture: dendritic tree complexity1
Decreased
Description: Mutants show reduced basal arborization complexity at 70110 micrometer from the cell body, compared to controls. mutants show reduced complexity of apical arbors at 180190 micrometer from the cell body compared to control mice.
Exp Paradigm: Ventral hippocampal ca1 pyramidal neurons that project to the bla were scored.
Description: Mutants show increased numbers of unprotected head dips while in the open arms of the elevated plus maze compared to controls. this increased head dipping is only partially explained by the increased time mutants spend in the open arms. mutants show no change in the number of head dips while in the closed arms compared to controls.
Exp Paradigm: NA
Description: Mutants enter the open arms more frequently and spend more time in the open arms than controls. mutants show no difference in the number of entries into the closed arms or time spent in the closed arms compared to controls.
Exp Paradigm: NA
Dendritic architecture: dendritic tree complexity1
Increased
Description: Stressed mutants show increased basal dendritic arbor complexity compared to control mice.
Exp Paradigm: Ventral hippocampal ca1 pyramidal neurons that project to the bla were scored.
Description: Stressed mutants show increased basal dendritic length of hippocampal ca1 neurons compared to controls.
Exp Paradigm: Ventral hippocampal ca1 pyramidal neurons that project to the bla were scored.
Description: Stressed mutants show increased numbers of unprotected head dips while in the open arms of the elevated plus maze compared to controls. this increased head dipping is only partially explained by the increased time mutants spend in the open arms. stressed mutants show no change in the number of head dips while in the closed arms compared to controls.
Exp Paradigm: NA
Description: Stressed mutants show reduced number of initiations of adult interactions with juveniles compared to controls. stressed mutants show no change in the duration of adult interactions with juveniles compared to controls.
Exp Paradigm: Same-sex juvenile 129s1/svimj mice were used as stimuli.
Description: Stress mutants enter the open arms more frequently and spend more time in the open arms than controls. stressed mutants show no difference in the number of entries into the closed arms or time spent in the closed arms compared to controls.
Exp Paradigm: Time spent in the open arm, number of open-arm entries, and head dips were scored.
Cued or contextual fear conditioning: memory of context1
Decreased
Description: Stressed mutants show decrease in the number and duration of freezing 24 hours after the training phase of the fear conditioning test compared to controls, indicating reduction in contextual fear memory.
Exp Paradigm: NA
Description: Marked size reduction of the liver, damage of the liver parenchyma, and defects in placental development
Exp Paradigm: Dissection followed by histological analysis.
Description: Complete absence of myotubes, muscle fibers, and myosin-expressing cells in limbs, shoulders and diaphgragm.
Exp Paradigm: Histological analysis using haematoxylin and eosin staining; immunofluroscence analysis.
Description: The size of the placenta is significantly reduced in embryos between e12.5 and e16.5. the size of the liver is also reduced.
Exp Paradigm: General observations
Description: Muscles that originate from migratory precursors, like those in the tip of the tongue, diaphragm and forelimbs are absent in e 15.5 embryos. it is determined that muscle precursors do not migrate out from the somites at e10.
Exp Paradigm: Whole mount in situ hybridization towards myod gene to test myogenic differentiation
Description: Significantly increased embryonic lethality is observed in met double mutant embryos starting at e13.5, with no surviving embryos past e17.5
Exp Paradigm: General observations
Description: Lack of met binding to grb2 in these mutants leads to lack of secondary fibers even in the muscles that appear to be grossly normal, like the medial muscle of the tongue, back and intercosta and body wall muscles.
Exp Paradigm: Hematoxylin-eosin staining for histological analysis.
Description: The lack of link between methionine tyrosine kinase and grb2 leads to lethality several hours after birth, possibly due to respiratory failure.
Exp Paradigm: NA
Description: The met mutants have reduced muscles in the forearms with an increase in flexor muscles over extensors in forearm, resulting in the hyperflexed pheotype observed in new borns.
Exp Paradigm: Hematoxylin-eosin staining for histological analysis.
Description: Fetal myoblasts undergoing mitosis are significantly reduced in number in the intercostal muscles labeled between e15 and e15.5
Exp Paradigm: Myogenic proliferation
