TSHZ3

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

Teashirt homolog 3 is a protein that in humans is encoded by the TSHZ3 gene.{{cite web | title = Entrez Gene: TSHZ3 teashirt family zinc finger 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57616}} In mice, it is a necessary part of the neural circuitry that controls breathing. The gene is also a homolog of the Drosophila melanogaster teashirt gene, which encodes a zinc finger transcription factor important for development of the trunk.{{cite journal | vauthors = Fasano L, Röder L, Coré N, Alexandre E, Vola C, Jacq B, Kerridge S | title = The gene teashirt is required for the development of Drosophila embryonic trunk segments and encodes a protein with widely spaced zinc finger motifs | journal = Cell | volume = 64 | issue = 1 | pages = 63–79 | date = January 1991 | pmid = 1846092 | doi = 10.1016/0092-8674(91)90209-h | s2cid = 39211509 }}

Tshz3-knockout mice 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 neurons 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.{{cite journal | vauthors = Caubit X, Thoby-Brisson M, Voituron N, Filippi P, Bévengut M, Faralli H, Zanella S, Fortin G, Hilaire G, Fasano L | display-authors = 6 | title = Teashirt 3 regulates development of neurons involved in both respiratory rhythm and airflow control | journal = The Journal of Neuroscience | volume = 30 | issue = 28 | pages = 9465–76 | date = July 2010 | pmid = 20631175 | pmc = 6632443 | doi = 10.1523/JNEUROSCI.1765-10.2010}}*{{lay source |template = cite web|vauthors = de Lange C |url = https://www.newscientist.com/article/dn19218-single-gene-could-be-key-to-a-babys-first-breath.html|title = Single gene could be key to a baby's first breath|date = July 23, 2010 |website = New Scientist }}

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.

{{cite journal | vauthors = Caubit X, Gubellini P, Andrieux J, Roubertoux PL, Metwaly M, Jacq B, Fatmi A, Had-Aissouni L, Kwan KY, Salin P, Carlier M, Liedén A, Rudd E, Shinawi M, Vincent-Delorme C, Cuisset JM, Lemaitre MP, Abderrehamane F, Duban B, Lemaitre JF, Woolf AS, Bockenhauer D, Severac D, Dubois E, Zhu Y, Sestan N, Garratt AN, Kerkerian-Le LG, Fasano L | display-authors = 6 | title = TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons | journal = Nature Genetics | volume = 48 | issue = 11 | pages = 1359–1369 | date = November 2016 | pmid = 27668656 | pmc = 5083212 | doi = 10.1038/ng.3681 }}

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.{{cite journal | vauthors = Chabbert D, Caubit X, Roubertoux PL, Carlier M, Habermann B, Jacq B, Salin P, Metwaly M, Frahm C, Fatmi A, Garratt AN, Severac D, Dubois E, Kerkerian-Le Goff L, Fasano L, Gubellini P | display-authors = 6 | title = Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder-like Behavior | journal = Biological Psychiatry | volume = 86 | issue = 4 | pages = 274–285 | date = August 2019 | pmid = 31060802 | doi = 10.1016/j.biopsych.2019.03.974 | s2cid = 85532974 | doi-access = free }}