TSHZ3 explained

Teashirt homolog 3 is a protein that in humans is encoded by the TSHZ3 gene.^[1] 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.^[2]

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.^[3]

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.^[4]

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.^[5]

Further reading

• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . November 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S . 6 . The LIFEdb database in 2006 . Nucleic Acids Research . 34 . Database issue . D415-8 . January 2006 . 16381901 . 1347501 . 10.1093/nar/gkj139 .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . 6 . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–44 . October 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .
• Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW . 6 . Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation . Nature Biotechnology . 22 . 6 . 707–16 . June 2004 . 15146197 . 10.1038/nbt971 . 27764390 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . 6 . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Research . 11 . 3 . 422–35 . March 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . November 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Nagase T, Kikuno R, Ishikawa K, Hirosawa M, Ohara O . Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 7 . 2 . 143–50 . April 2000 . 10819331 . 10.1093/dnares/7.2.143 . free .

Notes and References

1. Web site: Entrez Gene: TSHZ3 teashirt family zinc finger 3.
2. Fasano L, Röder L, Coré N, Alexandre E, Vola C, Jacq B, Kerridge S . The gene teashirt is required for the development of Drosophila embryonic trunk segments and encodes a protein with widely spaced zinc finger motifs . Cell . 64 . 1 . 63–79 . January 1991 . 1846092 . 10.1016/0092-8674(91)90209-h . 39211509 .
3. Caubit X, Thoby-Brisson M, Voituron N, Filippi P, Bévengut M, Faralli H, Zanella S, Fortin G, Hilaire G, Fasano L . 6 . Teashirt 3 regulates development of neurons involved in both respiratory rhythm and airflow control . The Journal of Neuroscience . 30 . 28 . 9465–76 . July 2010 . 20631175 . 6632443 . 10.1523/JNEUROSCI.1765-10.2010.
4. 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 . 6 . TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons . Nature Genetics . 48 . 11 . 1359–1369 . November 2016 . 27668656 . 5083212 . 10.1038/ng.3681 .
5. 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 . 6 . Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder-like Behavior . Biological Psychiatry . 86 . 4 . 274–285 . August 2019 . 31060802 . 10.1016/j.biopsych.2019.03.974 . 85532974 . free .