HELP     Sign In
Search

Relevance to Autism

Caubit et al., 2016 evaluated 7 new patients and 15 previously reported cases with 19q12-q13.11 deletions and determined that TSHZ3 lies within the minimal region of overlap for 19q12-q13.11 deletions found in patients with neurodevelopmental disorders, including ASD. Tshz3 +/- mice display altered corticostriatal synaptic transmission and plasticity and autism-like behavioral defects (Caubit et al., 2016).

Molecular Function

This gene encodes a zinc-finger transcription factor involved in developmental processes.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons.
ASD, ID
Support
Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder-like Behavior.
Support
Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.
ASD

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN850R001 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN850R002 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN850R003 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Multiplex 
 GEN850R004 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN850R005 
 copy_number_loss 
  
  
 Familial 
 Paternal 
  
 GEN850R006 
 copy_number_loss 
  
  
 Unknown 
  
  
 GEN850R007 
 intergenic_variant 
 C>T 
  
  
  
 Unknown 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
19
Duplication
 1
 
19
Duplication
 1
 
19
Deletion-Duplication
 11
 
19
Duplication
 2
 

Model Summary

Tshz3 null mice die at birth due to respiratory failure. Tshz3 heterozygous mice also display increased perinatal lethality, the ones that survive display increased repetitive behavior (digging and nose poking) and anxiety and impaired social approach and memory.

References

Type
Title
Author, Year
Primary
TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons.

M_TSHZ3_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Exon 2 of Tshz3 gene is replaced with a lacZ and neo cassette leading to a loss of TSHZ3 protein expression, after germline transmission the mice were bred to homozygosity.
Allele Type: Targeted (knockout, marker)
Strain of Origin:
Genetic Background: CD1
ES Cell Line:
Mutant ES Cell Line:
Model Source: PMID: 20631175

M_TSHZ3_2_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Exon 2 of Tshz3 gene is replaced with a lacZ and neo cassette leading to a loss of TSHZ3 protein expression, after germline transmission the heterozygous mice were maintained in a CD1 * CBA/H GNC background.
Allele Type: Targeted (knockout, marker)
Strain of Origin:
Genetic Background: CD1*CBA/H GNC
ES Cell Line:
Mutant ES Cell Line:
Model Source: PMID: 20631175

M_TSHZ3_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Mortality/lethality: neonatal1
Increased
Description: Tshz3 null embryos are unable to breathe at p0 and die with 100% penetrance
Exp Paradigm: NA
 Survival analysis
 P0
Gene expression1
Abnormal
Description: Tshz3 null embryos have several genes upregulated or downregulated in pathways involved in neuronal differentiation and axogenesis and show a diverse expression pattern as markers of different layers of cortical neurons
Exp Paradigm: NA
 Rna sequencing
 E18.5
Anatomical projections and connectivity1
 No change
 Immunostaining
 E18.5
Cortical lamination1
 No change
 Immunostaining
 E18.5
Neuronal number1
 No change
 Immunostaining
 E18.5
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_TSHZ3_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic plasticity: striatal ltp1
Increased
Description: Striatal ltp is enhanced in slices from tshz3 hets compared to slices from controls
Exp Paradigm: NA
 Whole-cell patch clamp
 P21-28
Presynaptic function: paired-pulse facilitation1
Decreased
Description: Paired pulse ration of ampa receptor mediated excitatory postsynaptic currents is lower in msns from tshz3 hets compared to littermate controls
Exp Paradigm: NA
 Whole-cell patch clamp
 P21-28
Repetitive digging1
Increased
Description: Tshz3 hets have display increased digging in the marble-burying test
Exp Paradigm: NA
 Marble-burying test
 2.5-3 months
Repetitive nose pokes1
Increased
Description: Tshz3 hets performed a higher number of stereotyped dips even when the total number of nose dips was similar to controls
Exp Paradigm: NA
 Hole-board test
 2.5-3 months
Social memory1
Decreased
Description: Tshz3 hets show no preference for novel stimulus mouse over familiar mouse
Exp Paradigm: NA
 Three-chamber social approach test
 2.5-3 months
Social approach1
Decreased
Description: Tshz3 hets show no preference for stimulus mouse over object in the modified three chamber test for social approach
Exp Paradigm: NA
 Three-chamber social approach test
 2.5-3 months
Urinary system development1
Decreased
Description: Tshz3 hets have increased presentation of unilateral hydroureter (about one fourth of embryos starting at e16.5)
Exp Paradigm: NA
 Histology
 >e16.5
Mortality/lethality: neonatal1
Increased
Description: Tshz3 hets show increased neonatal lethality which is reported to be 100% in c57bl/6 background and around 50% in cd1/cba/h gnc background
Exp Paradigm: NA
 Survival analysis
 P0-p10
Anxiety1
Increased
Description: Tshz3 hets display increased anxiety in parameters measured in two tests, including reduced time spent in the central zone of the open field and in the open arms of the elevated plus maze
Exp Paradigm: Open field test
 Open field test
 2.5-3 months
Anxiety1
Increased
Description: Tshz3 hets display increased anxiety in parameters measured in two tests, including reduced time spent in the central zone of the open field and in the open arms of the elevated plus maze
Exp Paradigm: Elevated plus maze test
 Elevated plus maze test
 2.5-3 months
Exploratory activity1
Decreased
Description: Tshz3 hets display reduced exploratory activity in the open field test assessed by number of zone crossings
Exp Paradigm: NA
 Open field test
 2.5-3 months
Exploratory activity: habituation1
 No change
 Three-chamber social approach test
 2.5-3 months
Olfactory learning and memory1
 No change
 Olfactory habituation-dishabituation test
 2.5-3 months
General locomotor activity: ambulatory activity1
 No change
 Open field test
 2.5-3 months
Anatomical projections and connectivity1
 No change
 Neuronal tracing
 1.6 months
Action potential property: firing rate1
 No change
 Whole-cell patch clamp
 P21-28
Intrinsic membrane properties1
 No change
 Whole-cell patch clamp
 P21-28
Spontaneous post synaptic event amplitude: excitatory currents1
 No change
 Whole-cell patch clamp
 P21-28
Spontaneous post synaptic event frequency: excitatory currents1
 No change
 Whole-cell patch clamp
 P21-28
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission1
 No change
 Whole-cell patch clamp
 P21-28
Ear twitch reflex or preyer's reflex1
 No change
 Preyer's reflex test
 2.5-3 months
Visual placing reflex1
 No change
 Visual placing test
 2.5-3 months
 Not Reported: Circadian sleep/wake cycle, Communications, Immune response, Maternal behavior, Molecular profile, Physiological parameters, Seizure

 

No Interactions Available
HELP
Copyright © 2017 MindSpec, Inc.