Mice with brain-specific deletion of the Chd5 gene (Chd5 -/-) displayed dendritic alterations in cortical pryamidal neurons, abnormalities in socialization and communication, and deficits in behavioral measures of empathy (Pisansky et al., 2017). A de novo damaging missense variant in the CHD5 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014.
Molecular Function
This gene encodes a member of the chromodomain helicase DNA-binding protein family. Members of this family are characterized by a chromodomain, a helicase ATP-binding domain and an additional functional domain. This gene encodes a neuron-specific protein that may function in chromatin remodeling and gene transcription.
The forebrains of Chd5 homozygous knockout mice show altered gene expression of genes important in cellular development and signaling. Chd5 homozygous knockout mice exhibit abnormal social and communicative behavior and a decreased preference for novelty. Chd5 homozygous knockout mice show deficits in responding to the distress of a conspecific, but no change in explicit direct fear conditioning.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exon 2 of the Chd5 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: Genetic Background: C57BL/6 J
ES Cell Line: C57BL/6 J
Mutant ES Cell Line: C57BL/6 J
Model Source: EUCOMM consortium
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Conditional heterozygous deletion of exon 2 of the Chd5 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: Genetic Background: C57BL/6 J
ES Cell Line: C57BL/6 J
Mutant ES Cell Line: C57BL/6 J
Model Source: EUCOMM consortium
Description: Mutant observer mice exhibited less freezing during foot shock conditioning of familiar demonstrator mice compared to wild-type observer mice that froze more during foot shock conditioning of the demonstrator mice, and this behavior was greater for observers that were siblings and cagemates of demonstrators and thereby familiar. this effect was not because of changes in usvs emitted by the demonstrator mice. activity measurements of mutant and control observer mice, recorded either 0-5 s or 5-60 s after demonstrator conditioning indicated equivalent initial immobility but sustained freezing only in wild-type mice. familiar/mutant mice exhibited initial escape behavior during acclimation that was not maintained through conditioning whereas familiar/wild-type
Exp Paradigm: Foot shock applied to a demonstrator mouse elicits fear behavior in an observer mouse. freezing in observer mice was measured using a load cell transducer system, which measures force-generated locomotor activity concurrent with demonstrator conditioning.
Description: Mutant pups produce fewer isolation induced usvs compared to controls. on p6, mutant pups produced fewer complex, frequency modulated usvs, compared to controls.
Exp Paradigm: NA
Description: Mutants show less overall investigation of novel olfactory stimuli, compared to controls.
Exp Paradigm: Mice were presented with control (water) odor followed by three distinct, successive odors (vanilla, female bedding, male bedding) of three trials each.
Description: Mutants show downregulation of genes involved in cellular growth and proliferation, cell death and survival, cell movement, dna replication, recombination, and repair, and up-regulation of genes involved in inter-cellular signaling and interaction, molecular transport, and, vitamin and mineral metabolism, compared to controls. 23 is regulated genes in the chd5 mutant matched with genes in the autismkb database.
Exp Paradigm: Rna sequencing
Description: Mutants show downregulation of genes involved in cellular growth and proliferation, cell death and survival, cell movement, dna replication, recombination, and repair, and up-regulation of genes involved in inter-cellular signaling and interaction, molecular transport, and, vitamin and mineral metabolism, compared to controls. 23 is regulated genes in the chd5 mutant matched with genes in the autismkb database.
Exp Paradigm: Quantitative pcr (qrt-pcr)
