Jump to content

TSHZ3

From Wikipedia, the free encyclopedia
TSHZ3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTSHZ3, TSH3, ZNF537, teashirt zinc finger homeobox 3
External IDsOMIM: 614119; MGI: 2442819; HomoloGene: 10835; GeneCards: TSHZ3; OMA:TSHZ3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_020856

NM_172298

RefSeq (protein)

NP_065907

NP_758502

Location (UCSC)Chr 19: 31.15 – 31.35 MbChr 7: 36.4 – 36.47 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Teashirt homolog 3 is a protein that in humans is encoded by the TSHZ3 gene.[5] 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.[6]

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.[7]

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 (Tshz3lacZ/+) show enrichment of ASD-related gene orthologs in the cerebral cortex, functional alterations of corticostriatal circuitry and ASD-relevant behavioral abnormalities. [8]

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.[9]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000121297Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021217Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: TSHZ3 teashirt family zinc finger 3".
  6. ^ Fasano L, Röder L, Coré N, Alexandre E, Vola C, Jacq B, Kerridge S (January 1991). "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. doi:10.1016/0092-8674(91)90209-h. PMID 1846092. S2CID 39211509.
  7. ^ Caubit X, Thoby-Brisson M, Voituron N, Filippi P, Bévengut M, Faralli H, et al. (July 2010). "Teashirt 3 regulates development of neurons involved in both respiratory rhythm and airflow control". The Journal of Neuroscience. 30 (28): 9465–76. doi:10.1523/JNEUROSCI.1765-10.2010. PMC 6632443. PMID 20631175.*Lay summary in: de Lange C (July 23, 2010). "Single gene could be key to a baby's first breath". New Scientist.
  8. ^ Caubit X, Gubellini P, Andrieux J, Roubertoux PL, Metwaly M, Jacq B, et al. (November 2016). "TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons". Nature Genetics. 48 (11): 1359–1369. doi:10.1038/ng.3681. PMC 5083212. PMID 27668656.
  9. ^ Chabbert D, Caubit X, Roubertoux PL, Carlier M, Habermann B, Jacq B, et al. (August 2019). "Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder-like Behavior". Biological Psychiatry. 86 (4): 274–285. doi:10.1016/j.biopsych.2019.03.974. PMID 31060802. S2CID 85532974.

Further reading

[edit]
[edit]
  • Overview of all the structural information available in the PDB for UniProt: Q63HK5 (Teashirt homolog 3) at the PDBe-KB.