WDTC1

WD and tetratricopeptide repeats 1
Identifiers
Symbol	WDTC1
NCBI gene	23038
HGNC	29175
RefSeq	NM_015023
UniProt	Q8N5D0
Other data
Locus	Chr. 1 p35.3

WDTC1 ("Adipose") is a gene associated with obesity.[1][2][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 Wdtc1^{tm1a(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]

*Wdtc1* knockout mouse phenotype
Characteristic	Phenotype
All data available at.[7][12]
Peripheral blood leukocytes 6 Weeks	Abnormal
Haematology 6 Weeks	Normal
Insulin	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Anti-nuclear Antibody Assay	Normal
Influenza Challenge	Abnormal

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References

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.
"ScienceDaily: 'Skinny Gene' Exists". Retrieved 2007-09-05.
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.
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.
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.
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.
"International Mouse Phenotyping Consortium".
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.
Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
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.
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.
"Infection and Immunity Immunophenotyping (3i) Consortium".
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.

External links

Born lucky: Scientists discover "skinny gene" - MSNBC

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[pmid17767906-1] 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.

[pmid19238144-3] 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.

[mgp_reference-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.

[IMPCsearch_ref-7] "International Mouse Phenotyping Consortium".

[pmid21677750-8] 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.

[mouse_library-9] Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-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.

[pmid23870131-11] 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.

[iii_ref-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.