IFITM3

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Interferon-induced transmembrane protein 3 (IFITM3) is a protein that in humans is encoded by the IFITM3 gene.[1][2][3] It plays a critical role in the immune system's defense against Swine Flu, where heightened levels of IFITM3 keep viral levels low, and the removal of IFITM3 allows the virus to multiply unchecked.[4] This observation has been further advanced by a recent study that shows that a single nucleotide polymorphism in the human IFITM3 gene purported to increase influenza susceptibility is overrepresented in people hospitalised with pandemic H1N1.[5] The prevalence of this mutation is thought to be approximately 1/400 in European populations.[5][6]


Model organisms

Model organisms have been used in the study of IFITM3 function. A conditional knockout mouse line, called Ifitm3tm1Masu[11][12] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[13][14][15]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty four tests were carried out on mutant mice, but no significant abnormalities were observed.[9] However, challenge with influenza A virus indicated that these mice display increased viral susceptibility.[5]

References

  1. ↑ Lewin AR, Reid LE, McMahon M, Stark GR, Kerr IM (Aug 1991). "Molecular analysis of a human interferon-inducible gene family". Eur J Biochem. 199 (2): 417–423. doi:10.1111/j.1432-1033.1991.tb16139.x. PMID 1906403.
  2. ↑ Tanaka SS, Yamaguchi YL, Tsoi B, Lickert H, Tam PP (Dec 2005). "IFITM/Mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primordial germ cell homing and repulsion". Dev Cell. 9 (6): 745–756. doi:10.1016/j.devcel.2005.10.010. PMID 16326387.
  3. ↑ "Entrez Gene: IFITM3 interferon induced transmembrane protein 3 (1-8U)".
  4. ↑ "Natural swine flu defence found".
  5. ↑ 5.0 5.1 5.2 Everitt A.R.; et al. (March 2012). "IFITM3 restricts the morbidity and mortality associated with influenza". Nature. 484 (7395): 519–23. doi:10.1038/nature10921. PMID 22446628.
  6. ↑ "Gene flaw linked to serious flu risk".
  7. ↑ "Salmonella infection data for Ifitm3". Wellcome Trust Sanger Institute.
  8. ↑ "Citrobacter infection data for Ifitm3". Wellcome Trust Sanger Institute.
  9. ↑ 9.0 9.1 9.2 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
  10. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  11. ↑ "International Knockout Mouse Consortium".
  12. ↑ "Mouse Genome Informatics".
  13. ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  14. ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  15. ↑ 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.
  16. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading