Low expression of a Ddm7/Ldm7-hybrid mutant (D/Ldm7) in the novel haplotype H-2nc identified in atopic dermatitis model NC/Nga mice
Low expression of a Ddm7/Ldm7-hybrid mutant (D/Ldm7) in the novel haplotype H-2nc identified in atopic dermatitis model NC/Nga mice
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在特应性皮炎模型 NC/Nga 小鼠中发现的新型单倍型 H-2nc 中 Ddm7/Ldm7 杂种突变体 (D/Ldm7) 的低表达
DOI：
10.1038/s41435-017-0003-y
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发表时间：
2019
期刊：
影响因子：
5
通讯作者：
Takahashi Kimimasa
中科院分区：
文献类型：
--
作者：
Ohkusu-Tsukada Kozo;Yamashita Tadashi;Tsukada Teruyo;Takahashi Kimimasa
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。然而，对AD模型小鼠NC/NGA的MHC类型(H_2单倍型)知之甚少。NC/NGA中CD8+或CD4+T细胞对各抗原提呈细胞(A/J：H-2a、C57BL/6：H-2b、BALB/c：H-2d或C3H/Hej：H-2k)有较强的反应性，提示NC/Nga具有不同的H2单倍型。目前，肿瘤坏死因子-α基因的多态微卫星(CA)重复序列因H2单倍型的不同而不同。NC/NGA(CA)n重复序列(n= 19)不同于其他被检株：A/J(n= 14)、BALB/c(n= 14)、C3 H/HeJ(n= 16)和C57BL/6(n= 20)。利用流式细胞术和基因分型，我们证明了NC/Nga H2单倍型具有独特的表型(Kd、I-Ak和I-Ek)，尽管检测到敏感的mRNA，但Dd和Ldk作为蛋白质缺乏。Ddm7和Ldm7的缺失是由于形成了一个独特的Ddm7/Ldm7-杂交突变体(D/Ldm7)所致。我们建议将这种新的H2单倍型称为“H-2nc”，并提供了关于使用NC/NGA小鼠进行AD研究的重要信息。
Environmental factors and the major histocompatibility complex (MHC) are involved in the pathogenesis of atopic dermatitis (AD). However, MHC type (H2haplotype) 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 otherH2haplotype. Polymorphic microsatellite (CA)nrepeats in TNF-α gene differ based on theH2haplotype at present. NC/Nga’s (CA)nrepeats (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 Ddand Ldlacked as protein despite sensitive mRNA detection. The loss of Ddand Ldwas caused by forming a unique Ddm7/Ldm7-hybrid mutant (D/Ldm7). We propose to call this novelH2haplotype the “H-2nc,” and provide the important information regarding the AD research using NC/Nga mice.