Sleeping Beauty Transposon Mutagenesis as a Tool for Gene Discovery in the NOD Mouse Model of Type 1 Diabetes
Colleen M Elso, Edward PF Chu, May A Alsayb, Leanne Mackin, Sean T Ivory, Michelle P Ashton, Stefan Broeer, Pablo A Silveira, Thomas C Brodnicki
G3-GENES GENOMES GENETICS | GENETICS SOCIETY AMERICA | Published : 2015
A number of different strategies have been used to identify genes for which genetic variation contributes to type 1 diabetes (T1D) pathogenesis. Genetic studies in humans have identified >40 loci that affect the risk for developing T1D, but the underlying causative alleles are often difficult to pinpoint or have subtle biological effects. A complementary strategy to identifying "natural" alleles in the human population is to engineer "artificial" alleles within inbred mouse strains and determine their effect on T1D incidence. We describe the use of the Sleeping Beauty (SB) transposon mutagenesis system in the nonobese diabetic (NOD) mouse strain, which harbors a genetic background predispose..View full abstract
Awarded by Peter Doherty Fellowship from the Australian National Health and Medical Research Council
Awarded by Juvenile Diabetes Research Foundation International
Awarded by Australian National Health and Medical Research Council
We thank J. Takeda and R. Plasterk for providing the transposon and transposase constructs used in this study, S. Foote for advice, and H. Dashnow for technical assistance. Transgenic NOD mice were generated by TheWalter & Eliza Hall Institute animal services facility. C.M.E was supported by Peter Doherty Fellowship 403037 from the Australian National Health and Medical Research Council. E.P.F.C. was supported by a Melbourne International Research Scholarship and St. Vincent's Institute Research Scholarship. M.P.A. was supported by an Australian Postgraduate Award. M.A.A. was supported by the Ministry of Higher Education Scholarship, Saudi Arabia. This work was funded by Innovative Grant 5-2007-620 from the Juvenile Diabetes Research Foundation International (T.C.B.), Project Grant 1030865 from the Australian National Health and Medical Research Council (T.C.B., P.S., C.M.E.), and the Victorian Government's Operational Infrastructure Support Program.