User:Rockpocket/MGP/SLX4

Model organisms
Model organisms have been used in the study of SLX4 function. A conditional knockout mouse line, called Slx4tm1a(EUCOMM)Wtsi 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.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.

Twenty four tests were carried out on mutant mice and ten significant abnormalities were observed. 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. This and further analysis revealed the mouse phenotype to model the human genetic illness, Fanconi anemia, and this was confirmed when patients with the disease were confirmed to have mutations in their SLX4 gene.