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Subcongenic analysis of genetic basis for impaired development of invariant NKT cells in NOD mice

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Abstract

Reduced numbers and function of invariant NKT (iNKT) cells partially contribute to type 1 diabetes (T1D) development in NOD mice. Previous linkage analysis identified a genetic locus on chromosome 2 controlling numbers of thymic iNKT cells. Interestingly, this locus resides within the Idd13 region that distinguishes NOD mice from the closely genetically related, but strongly T1D-resistant NOR strain. Thus, we tested if a genetic variant that confers T1D resistance in NOR mice may do so by enhancing iNKT cell numbers. iNKT cells were enumerated by an α-GalCer analog loaded CD1d tetramer in NOD and NOR mice as well as in NOD stocks carrying NOR-derived congenic regions on chromosome 1, 2, or 4. Significantly, more thymic and splenic iNKT cells were present in NOR than NOD mice. The NOR-derived Idd13 region on chromosome 2 contributed the most significant effect on increasing iNKT cell numbers. Subcongenic analyses indicated that at least two genes within the Idd13 region regulate iNKT cell numbers. These results further define the genetic basis for numerical iNKT cell defects contributing to T1D development in NOD mice.

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Acknowledgements

This work was supported by National Institutes of Health grants DK46266 and DK51090; Cancer Center Support Grant CA34196; as well as by grants from the Juvenile Diabetes Research Foundation International.

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  1. Pablo A. Silveira

    Present address: Immunology and Inflammation Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia

Authors and Affiliations

  1. The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA

    Yi-Guang Chen, John P. Driver & David V. Serreze

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  1. Yi-Guang Chen
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  2. John P. Driver
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  3. Pablo A. Silveira
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Correspondence to David V. Serreze.

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Chen, YG., Driver, J.P., Silveira, P.A. et al. Subcongenic analysis of genetic basis for impaired development of invariant NKT cells in NOD mice. Immunogenetics 59, 705–712 (2007). https://doi.org/10.1007/s00251-007-0236-4

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  • DOI: https://doi.org/10.1007/s00251-007-0236-4

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