Deletion mutations in the EXT1 gene were detected in two boys from separate families presenting with hereditary multiple exostoses and autism associated with mental retardation (Li et al., 2002). Inactivation of the EXT1 gene in mice resulted in impairments in social interaction, expression of stereotyped, repetitive behavior, and impairments in ultrasonic vocalization, as well as some associated features (Irie et al., 2012).
Molecular Function
This gene encodes an endoplasmic reticulum-resident type II transmembrane glycosyltransferase involved in the chain elongation step of heparan sulfate biosynthesis. Appears to be a tumor suppressor. Mutations in this gene are responsible for multiple hereditary exostoses (an autosomal dominant disorder characterized by multiple projections of bone capped by cartilage), trichorhinophalangeal syndrome type II, and possibly chondrosarcoma.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Association of autism in two patients with hereditary multiple exostoses caused by novel deletion mutations of EXT1.
Heparan Sulfate is critical for normal functioning of glutamatergic synapses and its deficiency mediates socio-communicative deficits and stereotypies characteristic for autism.
References
Type
Title
Author, Year
Primary
Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of 5 untranslated region of exon 1 to intron downstream of exon 1 of Ext gene using CamkII-cre, in excitatory neurons of the forebrain
Allele Type: Conditional loss-of-function
Strain of Origin: Not specified
Genetic Background: C57BL/6
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Not specified
Description: Decreased frequency and amplitude of mepscs in bla pyramidal neurons
Exp Paradigm: Patch-clamp recordings on bla pyramidal neurons following stimulation of their cortical input with gabaa and nmda antagonists
Neuronal activation following behavioral stimulation1
Decreased
Description: Decreased levels f neuronal c-fos in basolateral and medial amygdala and ventral orbitofrontal cortex
Exp Paradigm: Immunohistochemical analysis using anti-cfos antibodies was performed on brains from mice exposed to separation-reunion, where after weaning littermates of same genotype are housed together (two at a time). on the day before testing, the mice were transferred to two separate cages and isolated for 12 h. on the next morning, one of the two mice was chosen randomly as the stimulus mouse, and the other was designated as the test mouse. in the test, the stimulus mouse was placed in the cage of the test mouse, and their behaviors were videorecorded for 5 min.
Description: Decreased input output curves of the ampa receptor-mediated epsc response
Exp Paradigm: Patch-clamp recordings on bla pyramidal neurons following stimulation of their cortical input with gabaa and nmda antagonists
Description: Decreased input output curve of compound excitatory postsynaptic currents (epscs)
Exp Paradigm: Patch-clamp recordings on bla pyramidal neurons following stimulation of their cortical input
Description: Increased head bobbing behavior into same hole along with tendency to perform consecutive head-dips of more than four repetitions
Exp Paradigm: Hole-board assay for repetitive behavior
Description: Decreased communication demonstrated by reduced number, duration, amplitude, richness and complexity of ultrasonic vocalizations (usv)
Exp Paradigm: Ultrasonic vocalizations emission in response to challenge with female odor
