WDTC1

WDTC1 ("Adipose") is a gene associated with obesity.[1][2][3]

WD and tetratricopeptide repeats 1
Identifiers
SymbolWDTC1
NCBI gene23038
HGNC29175
RefSeqNM_015023
UniProtQ8N5D0
Other data
LocusChr. 1 p35.3

WDTC1 is a gene that codes for a protein acting as a suppressor in lipid accumulation. WDTC1 protein consists of seven WD40 domains, three transient receptor potential channel protein-protein interaction domains, DDB1 binding elements, and a prenylated C-terminus.[4] Reduced expression or disruption of WDTC1 gene is associated with obesity, increased triglyceride accumulation, and adipogenesis. WDTC1 is a factor in a complex composed of DDB1, CUL4, and ROC1 that restricts transcription in adipogenesis. [5]

Model organisms

Model organisms have been used in the study of WDTC1 function. A conditional knockout mouse line called Wdtc1tm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[6] Male and female animals underwent a standardized phenotypic screen[7] to determine the effects of deletion.[8][9][10][11] Additional screens performed: - In-depth immunological phenotyping[12]

Studies of phenotype of mice showed that having a loss of an allele resulted in obesity and poor metabolic profiles. Transgenic expression of the WDTC1 gene in mice showed the opposite effect with mice having less adipose.[13]

References

  1. Suh JM, Zeve D, McKay R, Seo J, Salo Z, Li R, et al. (September 2007). "Adipose is a conserved dosage-sensitive antiobesity gene". Cell Metabolism. 6 (3): 195–207. doi:10.1016/j.cmet.2007.08.001. PMC 2587167. PMID 17767906.
  2. "ScienceDaily: 'Skinny Gene' Exists". Retrieved 2007-09-05.
  3. Lai CQ, Parnell LD, Arnett DK, García-Bailo B, Tsai MY, Kabagambe EK, et al. (March 2009). "WDTC1, the ortholog of Drosophila adipose gene, associates with human obesity, modulated by MUFA intake". Obesity. 17 (3): 593–600. doi:10.1038/oby.2008.561. PMC 2874970. PMID 19238144.
  4. Ducos E, Vergès V, Dugé de Bernonville T, Blanc N, Giglioli-Guivarc'h N, Dutilleul C (September 2017). "Remarkable Evolutionary Conservation of Antiobesity ADIPOSE/WDTC1 Homologs in Animals and Plants". Genetics. 207 (1): 153–162. doi:10.1534/genetics.116.198382. PMID 28663238.
  5. Groh BS, Yan F, Smith MD, Yu Y, Chen X, Xiong Y (May 2016). "The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase". EMBO Reports. 17 (5): 638–47. doi:10.15252/embr.201540500. PMC 5341520. PMID 27113764.
  6. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  7. "International Mouse Phenotyping Consortium".
  8. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, et al. (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  9. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  10. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  11. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. (July 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  12. "Infection and Immunity Immunophenotyping (3i) Consortium".
  13. Groh BS, Yan F, Smith MD, Yu Y, Chen X, Xiong Y (May 2016). "The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase". EMBO Reports. 17 (5): 638–47. doi:10.15252/embr.201540500. PMC 5341520. PMID 27113764.
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