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Genetic control of murine invariant natural killer T cells maps to multiple type 1 diabetes regions

Genes & Immunity volume 14, pages 380–386 (2013)Cite this article

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Abstract

Reduced frequency of invariant natural killer T (iNKT) cells has been indicated as a contributing factor to type 1 diabetes (T1D) development in NOD mice. To further understand the genetic basis of the defect, we generated (NOD × ICR)F2 mice to map genes that control iNKT-cell development. We determined frequencies of thymic and splenic iNKT cells, as well as the ratio of CD4-positive and -negative subsets in the spleens of 209 F2 males. Quantitative trait loci (QTL) analysis revealed five loci that exceed the significant threshold for the frequency of thymic and/or splenic iNKT cells on Chromosomes (Chr) 1, 5, 6, 12 and 17. Three significant loci on Chr 1, 4 and 5 were found for the ratio of CD4-positive and -negative splenic iNKT cells. Comparisons with previously known mouse T1D susceptibility (Idd) loci revealed two significant QTL peak locations, respectively, mapped to Idd regions on Chr 4 and 6. The peak marker location of the significant Chr 12 iNKT QTL maps to within 0.5 Mb of a syntenic human T1D locus. Collectively, our results reveal several novel loci controlling iNKT-cell development and provide additional information for future T1D genetic studies.

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Acknowledgements

We would like to thank Dr E Leiter and Dr D Serreze at The Jackson Laboratory for critical reading of the manuscript. We are also grateful to the NIH tetramer core facility for providing us CD1d tetramers. This work was supported by the National Institutes of Health grant DK077443 (to Y-G Chen), the American Diabetes Association grant 1-10-BS-26 (to Y-G Chen), and the Children’s Hospital of Wisconsin Foundation.

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  1. S-W Tsaih and S Khaja: These authors contributed equally to this work.

Authors and Affiliations

  1. Medical College of Wisconsin, Human and Molecular Genetics Center, Milwaukee, WI, USA

    S-W Tsaih, S Khaja, A E Ciecko, E MacKinney & Y-G Chen

  2. Department of Pediatrics, Medical College of Wisconsin, Max McGee National Research Center for Juvenile Diabetes, Milwaukee, WI, USA

    S Khaja, A E Ciecko, E MacKinney & Y-G Chen

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  1. S-W Tsaih
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Correspondence to Y-G Chen.

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Tsaih, SW., Khaja, S., Ciecko, A. et al. Genetic control of murine invariant natural killer T cells maps to multiple type 1 diabetes regions. Genes Immun 14, 380–386 (2013). https://doi.org/10.1038/gene.2013.32

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