Department of Veterinary Pathology, Nippon Veterinary and Life science University (NVLU), 1-7-1 Kyonan-cho, Musashino, Tokyo, Japan.
Department of Biochemistry, School of Veterinary Medicine Azabu University Sagamihara, Kanagawa, Japan.
Genes Immun. 2019 Jan;20(1):74-81. doi: 10.1038/s41435-017-0003-y. Epub 2017 Dec 22.
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-2, C57BL/6: H-2, BALB/c: H-2, or C3H/HeJ: H-2), suggesting that NC/Nga has other H2 haplotype. Polymorphic microsatellite (CA) repeats in TNF-α gene differ based on the H2 haplotype at present. NC/Nga's (CA) 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 (K, I-A, and I-E) in which D and L lacked as protein despite sensitive mRNA detection. The loss of D and L was caused by forming a unique D/L-hybrid mutant (D/L). We propose to call this novel H2 haplotype the "H-2," and provide the important information regarding the AD research using NC/Nga mice.
环境因素和主要组织相容性复合体 (MHC) 参与了特应性皮炎 (AD) 的发病机制。然而，AD 模型小鼠 NC/Nga 的 MHC 类型 (H2 单倍型) 仍不清楚。NC/Nga 中的同种反应性 CD8 或 CD4 T 细胞强烈响应于每个抗原呈递细胞 (A/J：H-2、C57BL/6：H-2、BALB/c：H-2 或 C3H/HeJ：H-2)，这表明 NC/Nga 具有其他 H2 单倍型。目前，TNF-α 基因中的多态性微卫星 (CA) 重复序列根据 H2 单倍型而有所不同。NC/Nga 的 (CA) 重复序列 (n=19) 与其他检查的菌株不同，A/J (n=14)、BALB/c (n=14)、C3H/HeJ (n=16) 和 C57BL/6 (n=20)。我们通过流式细胞术和基因分型证明，NC/Nga H2 单倍型具有独特的表型 (K、I-A 和 I-E)，尽管检测到敏感的 mRNA，但缺乏 D 和 L 蛋白。D 和 L 的缺失是由于形成独特的 D/L 杂种突变体 (D/L) 引起的。我们建议将这种新型 H2 单倍型称为“H-2”，并为使用 NC/Nga 小鼠进行 AD 研究提供重要信息。
