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