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Model organisms

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Model organisms have been used in the study of ARID4A function. A conditional knockout mouse line, called Arid4atm1a(EUCOMM)Wtsi[1][2] 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.[3][4][5] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[6][7]

Twenty five tests were carried out and nine phenotypes were reported. Fewer homozygous mutant embryos were identified during gestation than expected, and in a seperate study less than the predicted Mendelian ratio survived until weaning. Homozygous mutant male adults has a reduced body weight curve and a decreased grip strength. Homozygous mutant adults of both sexes had a decreased body weight as determined by DEXA, displayed vertebral fusion and had clinical chemistry abnormalities including hypoalbuminemia and decreased circulating fructosamine levels. They also had haematological defects and an increased NK cell number.[6]

References

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  1. ^ "International Knockout Mouse Consortium".
  2. ^ "Mouse Genome Informatics".
  3. ^ 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.
  4. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474: 262-263. doi:10.1038/474262a.{{cite web}}: CS1 maint: location (link) CS1 maint: year (link)
  5. ^ 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.{{cite book}}: CS1 maint: location (link) CS1 maint: location missing publisher (link) CS1 maint: multiple names: authors list (link) CS1 maint: year (link)
  6. ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Opthalmologica 88: 925-7.doi:10.1111/j.1755-3768.2010.4142.x: Wiley.{{cite web}}: CS1 maint: location (link)
  7. ^ 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. PMID 21722353.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  8. ^ "Body weight data for Arid4a". Wellcome Trust Sanger Institute.
  9. ^ "Grip strength data for Arid4a". Wellcome Trust Sanger Institute.
  10. ^ "DEXA data for Arid4a". Wellcome Trust Sanger Institute.
  11. ^ "Radiography data for Arid4a". Wellcome Trust Sanger Institute.
  12. ^ "Clinical chemistry data for Arid4a". Wellcome Trust Sanger Institute.
  13. ^ "Haematology data for Arid4a". Wellcome Trust Sanger Institute.
  14. ^ "Salmonella infection data for Arid4a". Wellcome Trust Sanger Institute.
  15. ^ "Citrobacter infection data for Arid4a". Wellcome Trust Sanger Institute.