Rare variants in the MDGA2 gene have been identified with autism (Bucan et al., 2009). In addition, MDGA2 has been found to have genetic association with neuroticism (van den Oord et al., 2008).
Molecular Function
The encoded protein is a member of the immunoglobulin domain cell adhesion molecule subfamily and and is proposed to be involved in regulating neuronal migration and axonal guidance
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes.
Homozygous Mdga2 knockout mice are perinatal lethal. Mdga2 heterozygous mice have increased asymmetric synapse density, mEPSC frequency and amplitude, and altered LTP, but no changes in inhibitory synapses. Mdga2 mice also demonstrate autism-like phenotype including stereotypy, aberrant social interactions, and impaired memory. The fMRI studies show Mdga2 heterozygous mice have increased cortical spontaneous actvity and intracortical functional connectivity. The abnormal cortical processing caused by Mdga2 deficiencies might result from the disruption of the Neurexin-Neuroligin interactions.
References
Type
Title
Author, Year
Additional
Altered Cortical Dynamics and Cognitive Function upon Haploinsufficiency of the Autism-Linked Excitatory Synaptic Suppressor MDGA2.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
The coding sequence of the first exon is replaced by a LacZ-pA-PGK-Neo-pA cassette.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: C57BL/6J
ES Cell Line: C57BL/6 and CBA (TT2)
Mutant ES Cell Line: Model Source: Riken
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
The coding sequence of the first exon is replaced by a LacZ-pA-PGK-Neo-pA cassette.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: C57BL/6J
ES Cell Line: C57BL/6 and CBA (TT2)
Mutant ES Cell Line: Model Source: Riken
Description: Increased perinatal lethalty in mdga2 knockout mice with c57bl6 background
Exp Paradigm: Genotypic ratio of p14 progeny from heterozygous parents
Genotypic ratio of progeny from heterozygous parents
Description: Mdga2 hets show slightly increased general locomotor activity relative to wild-type controls
Exp Paradigm: Home cage behavior: traveled distance
Description: Increased asymmetric (excitatory) synapse density in the ca1 stratum radiatum of mdga2 hets relative to wild-type controls
Exp Paradigm: Electron microscopy: hippocampal ca1 stratum radiatum
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission1
Decreased
Description: Decreased ratio of nmdar- and ampar-dpendent (nmdar/ampar) transmisson in hets relative to wild-type controls
Exp Paradigm: Whole-cell patch clamp: ca1 pyramidal cells
Description: Increased fepsp response to the stimulation in mdga2 hets relative to wild-type controls
Exp Paradigm: Field potential recordings versus the injected current intensity or measured presynaptic fiber volley amplitude: hippocampal sc-ca1 pathway (schaffer collateral axonal fibers - ca1)
Description: Mdga2 hets have no change in the depletion rate of the readily releasable vesicle pool but have increased depletion rate of reserve pool vesicles of the hippocampal neurons relative to wild-type controls
Exp Paradigm: Field potential recordings: hippocampal sc-ca1 pathway (schaffer collateral axonal fibers - ca1)
Description: Mdga2 hets exhibit significantly higher levels of baseline activity than wild-type controls in posterior segment of secondary motor cortex (pm2), retrosplenial cortex (rs), primary motor cortex for c2 whisker (mbc), and forelimb motor cortex (mfl)
Exp Paradigm: Functional magnetic resonance imaging (fmri)-resting state: voltage-sensitive dye (vsd) imaging
Functional magnetic resonance imaging (fmri)-resting state
Description: Mdga2 hets have increased inanimate object preference relative to wild-type controls
Exp Paradigm: Novel object exploration test: the time mice explored either one of the novel objects (different shapes) was calculated as a ratio of total time
Description: Mdga2 hets display impaired spatial learning with normal willingness and swim ability
Exp Paradigm: Morris water maze test: hidden-platform
Description: Mdga2 hets show no preference for the novel object over a familiar object
Exp Paradigm: Novel object exploration test: fraction of time exploring the novel object at both 30 min and 24 hr after the training session
Cued or contextual fear conditioning: memory of context: long term recall1
Decreased
Description: Mdga2 hets have decreased long term memory recall in contextual fear conditioning tests
Exp Paradigm: Fear conditioning test: contextual memory at 24 hours or 7 days after training
Description: Increased protein levels of psd-95 family maguks or nlgn1 in the ca1 and pfc or ca1 of mdga2 hets, respectively, relative to the wild-type littermate controls
Exp Paradigm: Western blot: ca1: maguks, nlgn1; western blot: pfc: maguks
