Teashirt homolog 3 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''TSHZ3''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
In mice, it is a necessary part of the neural circuitry that controls breathing. The gene is also a homolog of the
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
teashirt gene, which encodes a
zinc finger
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
important for development of the trunk.
''Tshz3''-
knockout mice
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
do not develop the respiratory rhythm generator (
RRG) neural circuit, which is a pacemaker that produces an oscillating rhythm in the brainstem and controls autonomous breathing. The RRG
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa ...
s are present, but are abnormal. Those mice do not survive because they don't initiate breathing after birth. ''Tshz3'' is being studied for its relationship to infant breathing defects in humans.
[*]
''TSHZ3'' has been identified as a critical region for a syndrome associated with heterozygous deletions at 19q12-q13.11, which includes autism spectrum disorder (ASD) symptoms such autistic traits, speech disturbance and intellectual disability, as well as renal tract abnormalities. Mice with heterozygous ''Tshz3'' deletion (''Tshz3
lacZ''
/+) show enrichment of ASD-related gene orthologs in the cerebral cortex, functional alterations of corticostriatal circuitry and ASD-relevant behavioral abnormalities.
Postnatal conditional deletion of ''Tshz3'' in mouse induces behavioral deficits mimicking ASD, as well as abnormalities in synaptic transmission and plasticity in the corticostriatal circuit. These changes are associated to dysregulation of the cortical expression of more than 1000 genes, in particular coding for synaptic components, half of which has human orthologues involved in ASD.
References
Further reading
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External links
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