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Low expression of a Ddm7/Ldm7-hybrid mutant (D/Ldm7) in the novel haplotype H-2nc identified in atopic dermatitis model NC/Nga mice

Abstract

Environmental factors and the major histocompatibility complex (MHC) are involved in the pathogenesis of atopic dermatitis (AD). However, MHC type (H2 haplotype) of AD model mice NC/Nga is poorly understood. Alloreactive CD8+ or CD4+ T cells in NC/Nga strongly responded to each antigen-presenting cells (A/J: H-2a, C57BL/6: H-2b, BALB/c: H-2d, or C3H/HeJ: H-2k), suggesting that NC/Nga has other H2 haplotype. Polymorphic microsatellite (CA)n repeats in TNF-α gene differ based on the H2 haplotype at present. NC/Nga’s (CA)n repeats (n = 19) were different from other examined strains, A/J (n = 14), BALB/c (n = 14), C3H/HeJ (n = 16), and C57BL/6 (n = 20). Using flow cytometry and genotyping, we demonstrated the NC/Nga H2 haplotype had a unique phenotype (Kd, I-Ak, and I-Ek) in which Dd and Ld lacked as protein despite sensitive mRNA detection. The loss of Dd and Ld was caused by forming a unique Ddm7/Ldm7-hybrid mutant (D/Ldm7). We propose to call this novel H2 haplotype the “H-2nc,” and provide the important information regarding the AD research using NC/Nga mice.

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Acknowledgements

We thank Dr. Tohei (NVLU) for microbiological monitoring tests of mice, Dr. Hakamata (NVLU) for management of full-barrier animal facility, and Dr. Yokosuka (NVLU) for welfare of laboratory animal research.

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Correspondence to Kozo Ohkusu-Tsukada.

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Ohkusu-Tsukada, K., Yamashita, T., Tsukada, T. et al. Low expression of a Ddm7/Ldm7-hybrid mutant (D/Ldm7) in the novel haplotype H-2nc identified in atopic dermatitis model NC/Nga mice. Genes Immun 20, 74–81 (2019). https://doi.org/10.1038/s41435-017-0003-y

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