Autoimmune experimental orchitis and chronic glomerulonephritis with end stage renal disease are controlled by Cgnz1 for susceptibility to end organ damage.
Autoimmune experimental orchitis and chronic glomerulonephritis with end stage renal disease are controlled by Cgnz1 for susceptibility to end organ damage.
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自身免疫性实验性睾丸炎和慢性肾小球肾炎伴终末期肾病受Cgnz 1控制，对终末器官损害敏感。
DOI：
10.1016/j.clim.2021.108675
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发表时间：
2021-03
期刊：
影响因子：
--
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中科院分区：
文献类型：
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NZM 2328中1号染色体上的Cgnz 1定位于1号染色体的1.34 Mb区域，使免疫复合物（IC）介导的肾小球肾炎（GN）在雌性小鼠中从急性GN（aGN）进展为慢性GN（cGN），伴有严重蛋白尿和终末期肾病。该基因座介导足细胞对IC介导的损伤的易感性。利用已发表的观察结果，即Cgnz 1来源于NZW，并且NZW易患睾丸炎、附睾炎和输精管炎，而C57 L/J对这些疾病具有抗性，研究了该遗传区域也赋予生殖细胞在活动性实验性自身免疫性睾丸炎（EAO）模型中易受无精子发生和不育损伤的可能性。对来自多个染色体内（1号染色体）重组株的雄性小鼠进行CFA中精子匀浆免疫接种，同时给予百日咳博德特氏菌毒素。在NZM 2328及其从C57 L/J渗入到NZM 2328的具有不同1号染色体遗传间隔的同源株中，从aGN进展到cGN、严重蛋白尿和终末期肾病与EAO的易感性一致。耐药株和敏感株的抗睾丸抗体和抗精子抗体相当。因此，决定EAO易感性的遗传间隔与Cgnz 1相同，并定位于染色体1的1.34 Mb区域。该区域可能赋予男性性腺中的生殖细胞易受免疫介导的炎症损伤的能力。该区域暂时更名为Cgnz 1/Eaoz 1。这些观察结果进一步强调了终末器官对损伤的易感性在全身性和器官特异性自身免疫性疾病的发病机制中的重要性。
Cgnz1 on chromosome 1 mapped into a 1.34 Mb region of chromosome 1 in NZM2328 confers the progression of immune complex (IC)-mediated glomerulonephritis (GN) from acute GN (aGN) to chronic GN (cGN) with severe proteinuria and end stage renal disease in female mice. This genetic locus mediates podocyte susceptibility to IC-mediated damage. Taking advantage of the published observation that Cgnz1 is derived from NZW and that NZW is susceptible to orchitis, epididymitis and vasitis while C57L/J is resistant to these diseases, the possibility that this genetic region also confers germ cells susceptible to damage with aspermatogenesis and sterility in an active experimental autoimmune orchitis (EAO) model was investigated. Male mice from multiple intrachromosome (chromosome 1) recombinant strains were subjected to immunization with a sperm homogenate in CFA with concomitant administration of Bordetella pertussis toxin. There was concordance of the progression from aGN to cGN, severe proteinuria and end stage renal disease with susceptibility of EAO in NZM2328 and its congenic strains with various chromosome 1 genetic intervals introgressed from C57L/J to NZM2328. Both resistant and susceptible strains made comparable anti-testis and anti-sperm Abs. Thus the genetic interval that determines susceptibility to EAO is identical to that of Cgnz1 and mapped to the 1.34 Mb region in chromosone 1. This region likely confers germ cells in the male gonad susceptible to damage by immunologically mediated inflammation. This region has been tentatively renamed Cgnz1/Eaoz1. These observations further emphasize the importance of end organ susceptibility to damage in the pathogenesis of both systemic and organ specific autoimmune diseases.
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DOI：
10.1084/jem.20130731
发表时间：
2013-10-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ge Y;Jiang C;Sung SS;Bagavant H;Dai C;Wang H;Kannapell CC;Cathro HP;Gaskin F;Fu SM
通讯作者：
Fu SM
影响因子：
19.6
作者：
Krolewski AS;Skupien J;Rossing P;Warram JH
通讯作者：
Warram JH
DOI：
10.1016/j.clim.2014.06.008
发表时间：
2014-09
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Dai C;Wang H;Sung SS;Sharma R;Kannapell C;Han W;Wang Q;Davidson A;Gaskin F;Fu SM
通讯作者：
Fu SM
DOI：
10.1073/pnas.92.12.5684
发表时间：
1995-06-06
影响因子：
11.1
作者：
MEEKER, ND;HICKEY, WF;TEUSCHER, C
通讯作者：
TEUSCHER, C
狼疮性肾小球炎的发病机理不需要对双链DNA，核小体和其他核抗原的破坏耐受性。
影响因子：
15.3
作者：
Waters, ST;McDuffie, M;Bagavant, H;Deshmukh, US;Gaskin, F;Jiang, C;Tung, KSK;Fu, SM
通讯作者：
Fu, SM