Genetic association has been found between the TPH2 gene and autism in a Caucasian (from US and Italy) population cohort (Coon et al., 2005). However, other studies have found no genetic association between the TPH2 gene and autism in Italian, Caucasian-American and other population cohorts. Separately, genetic association has been found between the TPH2 gene and unipolar major depression in a US population cohort.
Molecular Function
The encoded protein has tryptophan 5-monooxygenase activity.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Possible association between autism and variants in the brain-expressed tryptophan hydroxylase gene (TPH2).
Case Report: Whole Exome Sequencing Revealed Disease-Causing Variants in Two Genes in a Patient With Autism Spectrum Disorder, Intellectual Disability, Hyperactivity, Sleep and Gastrointestinal Distur
Tph2 nul mice have no brain TPH2 protein, therefore lack brain serotonin. They exhibit deficiencies in social interaction and ultrasonic vocalization and increase in repetitive behavior.
References
Type
Title
Author, Year
Primary
Mice genetically depleted of brain serotonin display social impairments, communication deficits and repetitive behaviors: possible relevance to aut...
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A neo cassete replaced 109 bp of exon 1 of the Tph2 gene, no brain Tph2 protein is detectable in the nullmice.
Allele Type: Targeted(knockout)
Strain of Origin: Genetic Background: C57BL/6*Sv129
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A deletion of 5.2 kb region containing the coding region of exon 1 and 2 of the TPh2 gene, resulting in a complete disabling of transcription and translation of the Tph2 gene in homozygous mice.
Allele Type: Targeted(knockout/marker)
Strain of Origin: Genetic Background: C57BL/6
ES Cell Line: E14tg2A
Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
A deletion of 5.2 kb region containing the coding region of exon 1 and 2 of the Tph2 gene, resulting in a complete disabling of transcription and translation of Tph2 gene in targeted chromosome.
Allele Type: Targeted(knockout/marker)
Strain of Origin: Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source:
Description: Tph2 null pups take longer to correctly display negative geotaxis, monitored as a development milestone checked within the first two weeks of life, compared to wild type control pups
Exp Paradigm: NA
Description: Tph2 null pups take longer to develop the righting reflex , monitored as a development milestone checked within the first two weeks of life, compared to wild type control pups
Exp Paradigm: NA
Description: Tph2 null adult mice show reduced sociall memory as they fail to differentiate between a novel stimulus mouse compared to a familiar stimulus mouse, unlike wild type adult controls
Exp Paradigm: NA
Description: Tph2 male adults display reduced urine marking (stimulation( in response to stimulus scent from female mice in estrous, compared to wild type male mice. this is considered to be analogous to reduced social interaction or response to opposite sex by the authors
Exp Paradigm: Males only
Description: Tph2 null pups have reduced recognition of maternal scent compared to wild type pups, tested in an assay where the choice to sniff maternal scent (in litter) over stranger dam scent, distributed in separate locations in a polycarbonate cage, was measured in p14 pups.
Exp Paradigm: In a transparent polycarbonate cage litters from the mother, clean cage and stranger dams are placed in one corner, center and a third corner respectively. p14 pups were placed at the center, facing the two different scented litters, randomly, over three 1 min trials, with 10 s intervals and the time spent in each part of the cage was estimated
Description: Tph2 female (non aggressive subjects) show reduced reciprocal social interaction with age and sex matched stranger stimulus mice
Exp Paradigm: Females only
Description: Tph2 null adult mice have statistically significant decrease in preference for stranger mouse scent compared to adult wild type controls. tph2 null adults spend less time sniffing objects permeated with stranger mouse litter scent
Exp Paradigm: NA
Description: Tph2 null adults and weanling mice show reduced social dishabituation as they do not show increased interest towards a novel stimulus mouse in the dishabituation trial following the habituation trials, unlike wild type mice which show increased interest in a novel mouse
Exp Paradigm: Three trials of habituation with a familiar mouse, to check the amount of interaction with increasing habituation, followed by 1 trial for dishabituation with the introduciton of a novel stimulus mouse ( test and stimulus mice placed in adjacent cages)
Description: Overall, tph2 null mice have a delayed acquisition of several postnatal developlmental markers showing growth retardation, delayed acquisition of fur color and eye opening.
Exp Paradigm: NA
Description: Tph2 null mice have reduced interest:spend less time sniffing, in a novel object placed in an open field, compared to wild type controls, showing a reduction in exploratory activity
Exp Paradigm: NA
Description: Tph2 pups emit fewer isolation induced usvs compared to wild type controls at p6 ( this is the day wt pups emit the most usv calls). at this age they appear to emit similar usvs compared to heterozygous pups.
Exp Paradigm: NA
