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Identification of candidate genes that influence sex hormone-dependent disease phenotypes in mouse lupus.
Genes and Immunity ( IF 5.0 ) Pub Date : 2007-11-30 , DOI: 10.1038/sj.gene.6364447
M R Gubbels Bupp 1 , T N Jørgensen , B L Kotzin
Affiliation  

Ninety percent of systemic lupus erythematosus patients are female, and gender differences in lupus susceptibility are also observed in (New Zealand Black x New Zealand White)F1 (BWF1) lupus-prone mice. We followed orchiectomized, intact male and female BWF1 mice for lupus-like disease for 1 year. A comparative gene expression analysis was then used to identify candidate genes potentially responsible for gender-dependent differences in lupus susceptibility. Seven genes encoded on the sex chromosomes and 77 probe sets, including 14 immunoglobulin genes, encoded on the autosomal chromosomes were identified as differentially expressed in male versus female BWF1 splenocytes prior to disease onset. Five genes were determined to be regulated by either estradiol or dihydrotestosterone in an in vivo system and most of them were preferentially expressed in antigen-presenting cells. Gender differences in the expression of Csf3-r, Histh1c, Serpinb2, Slc6a4 and Cd22 in BWF1 mice are the result of transcriptional modification by sex hormones and warrant further investigation. The identification of candidate genes and their expression patterns in splenocyte sub-populations provide new information regarding the mechanisms by which sex hormones influence the development of mouse lupus.

中文翻译:

鉴定影响小鼠狼疮中性激素依赖性疾病表型的候选基因。

系统性红斑狼疮患者中有90%是女性,在(New Zealand Black x New Zealand White)F1(BWF1)易患狼疮的小鼠中也观察到了狼疮易感性的性别差异。我们追踪了经过睾丸切除的完整雄性和雌性BWF1小鼠的狼疮样疾病1年。然后,使用比较基因表达分析来鉴定可能导致狼疮易感性的性别依赖性差异的候选基因。在疾病发作之前,在性染色体上编码的七个基因和在常染色体上编码的77个探针集(包括14个免疫球蛋白基因)被鉴定为在男性和女性BWF1脾细胞中差异表达。确定了五个基因在体内系统中受雌二醇或二氢睾丸激素的调控,其中大多数基因优先在抗原呈递细胞中表达。BWF1小鼠中Csf3-r,Histh1c,Serpinb2,Slc6a4和Cd22表达的性别差异是性激素转录修饰的结果,有待进一步研究。脾细胞亚群中候选基因及其表达模式的鉴定为性激素影响小鼠狼疮的发育提供了新的信息。
更新日期:2019-11-01
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