User:Rockpocket/MGP/SLX4
Model organisms
[edit]Model organisms have been used in the study of SLX4 function. A conditional knockout mouse line, called Slx4tm1a(EUCOMM)Wtsi[1] 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.[2][3]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[4][5]
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Abnormal |
| Fertility | Abnormal |
| Body weight | Abnormal[6] |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Abnormal[7] |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Abnormal[8] |
| Radiography | Abnormal[9] |
| Body temperature | Normal |
| Eye morphology | Abnormal[10] |
| Clinical chemistry | Normal |
| Haematology | Abnormal[11] |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Abnormal |
| Heart weight | Abnormal[12] |
| Skin Histopathology | Normal |
| Brain histopathology | Normal |
| Salmonella infection | Normal[13] |
| Citrobacter infection | Normal[14] |
| All tests and analysis from[4] |
Twenty four tests were carried out on mutant mice and ten significant abnormalities were observed.[4] A viability at weaning study found less homozygous mutant were present than predicted by Mendelian ratio. Homozygous mutant animal of both sexes were sub-fertile and homozygous females had a reduced body weight, body length, heart weight, platelet count and lean mass. Homozygotes of both sex had abnormal eye sizes, narrow eye openings, skeletal defects (including scoliosis and fusion of vertebrae), and displayed an increase in DNA instability as shown by a micronucleus test.[4] This and further analysis revealed the mouse phenotype to model the human genetic illness, Fanconi anemia,[5][15] and this was confirmed when patients with the disease were confirmed to have mutations in their SLX4 gene. [16]
References
[edit]- ^ "International Knockout Mouse Consortium".
- ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351). Nature 474: 262-263. doi:10.1038/474262a: 262–263. doi:10.1038/474262a. PMID 21677718.
{{cite journal}}: CS1 maint: location (link) - ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1). Cell 128(1): 9-13. doi:10.1016/j.cell.2006.12.018 PMID 17218247: 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
{{cite journal}}: CS1 maint: location (link) CS1 maint: multiple names: authors list (link) - ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88. Acta Opthalmologica 88: 925-7.doi:10.1111/j.1755-3768.2010.4142.x: Wiley. doi:10.1111/j.1755-3768.2010.4142.x.
{{cite journal}}: CS1 maint: location (link) - ^ a b 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ "Body weight data for Slx4". Wellcome Trust Sanger Institute.
- ^ "Dysmorphology data for Slx4". Wellcome Trust Sanger Institute.
- ^ "DEXA data for Slx4". Wellcome Trust Sanger Institute.
- ^ "Radiography data for Slx4". Wellcome Trust Sanger Institute.
- ^ "Eye morphology data for Slx4". Wellcome Trust Sanger Institute.
- ^ "Haematology data for Slx4". Wellcome Trust Sanger Institute.
- ^ "Heart weight data for Slx4". Wellcome Trust Sanger Institute.
- ^ "Salmonella infection data for Slx4". Wellcome Trust Sanger Institute.
- ^ "Citrobacter infection data for Slx4". Wellcome Trust Sanger Institute.
- ^ Crossan GP, van der Weyden L, Rosado IV; et al. (February 2011). "Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia". Nat. Genet. 43 (2): 147–52. doi:10.1038/ng.752. PMC 3624090. PMID 21240276.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ Kim Y, Lach FP, Desetty R, Hanenberg H, Auerbach AD, Smogorzewska A (February 2011). "Mutations of the SLX4 gene in Fanconi anemia". Nat. Genet. 43 (2): 142–6. doi:10.1038/ng.750. PMC 3345287. PMID 21240275.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)