De novo frameshift variants in this gene have been identified in unrelated ASD cases from the Simons Simplex Collection (Iossifov et al., 2012; Dong et al., 2014).
Molecular Function
Histone methyltransferase that specifically mono- and dimethylates 'Lys-4' of histone H3 (H3K4me1 and H3K4me2). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.
Combined cohort consisting of 18,381 ASD cases and 27,969 controls from iPSYCH and the Psychiatric Genomic Consortium (PGC) used in the main GWAS analysis, and five cohorts of European ancestry including a total of 2,119 additional ASD cases and 142,379 controls
The Kmt2e haploinsufficiency model shows social deficits, repetitive behaviors and higher anxiety and depression. The model shows a decrease in neuronal activity in the amygdala, that is accompanied by an increase in neuronal size and number in the basolateral and basomedial amygdala.
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
KMT2E-deficient mice were generated by using CRISPR/Cas9 approach that produced an 8-nucleotide deletion followed by a stop codon in exon 3 of KMT2E.
Allele Type: Knockout
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Model Source: Dr. Zhang Yan (Shanghai Pasteur Institute of Chinese Academy of Sciences)
Description: Kmt2e mutant male and female mice exhibited a significant increase in the number of neurons in the basolateral amygdala nucleus compared to wildtype control males and females. Kmt2e mutant mice exhibited a significant increase in the number of neurons in the basomedial amygdala nucleus compared to wildtype controls. Male mutant mice displayed a significant increase, while female mutant mice did not.
Exp Paradigm: NeuN
Description: Kmt2e mutant mice exhibited significantly decreased anteroposterior (AP) length of the cerebral cortex and cortical area compared to wildtype control mice. Though not significant, cortical length displayed a decreasing trend compared to wildtype control mice.
Description: Kmt2e mutant male and female mice exhibited a significant increase in neuronal size in the basolateral amygdala nucleus compared to wildtype control males and females. Kmt2e mutant mice exhibited a significant increase in neuronal size in the basomedial amygdala nucleus compared to wildtype controls. Male mutant mice displayed a significant increase, while female mutant mice did not.
Exp Paradigm: NeuN
Description: Kmt2e mutant mice exhibited a significant decrease in normalized standard uptake value (SUV) in the amygdala and striatum compared to wildtype controls. Specifically, amygdala SUV in male mutant mice was significantly reduced, while amygdala SUV in female mutant mice and striatum SUV in male/female mutant mice showed decreasing trends.
Description: Kmt2e mutant mice spent similar amounts of time with a novel and familiar mouse during phase 3, while wildtype control mice spent more time with a novel mouse; wildtype mice had positive social preference score but the score was significantly decreased in mutant mice, demonstrating that wildtype mice had a social preference to novelty but mutant mice lost their social preference to novelty.
Exp Paradigm: phase 3: same age/gender/genotype-matched mouse as in phase 1 in chamber 1, novel gender/genotype-matched mouse in chamber 2
Description: Kmt2e mutant male and female mice exhibited a decrease in the amount of time spent in the chamber containing a littermate of the same genetic background and same sex compared to wildtype controls, as further evidenced by significantly decreased social preference scores in total and female mutant mice compared to wildtype controls.
Description: Although Kmt2e mutant male and female mice exhibited no difference in preference for either chamber during phase 1 of the social approach test compared to wildtype controls, during phase 2, mutant mice exhibited significantly reduced social time with an age/gender/genotype-matched mouse. This was further demonstrated by a trend towards a reduced social preference score compared to WT mice.
Exp Paradigm: phase 1: non-social object in both chambers; phase 2: age/gender/genotype-matched mouse in chamber 1, non-social object in chamber 2
Description: Kmt2e mutant male and female mice spent significantly less time in the central zone and displayed fewer entries of the central zone compared to wildtype control males and females.
