Interspecies Comparative Genomics Identifies Optimal Mouse Models of Scleroderma (bleoskin)

Systemic sclerosis (SSc) is confounded by considerable disease heterogeneity. Animal models of SSc that recapitulate distinct subsets of disease at the molecular level have not delineated. We applied interspecies comparative analysis of genomic data from multiple mouse models of SSc and patients with SSc to determine which animal models best reflect the SSc intrinsic gene expression subsets. Gene expression measured in skin from mice with sclerodermatous graft-versus-host disease, bleomycin-induced fibrosis, or Tsk1/+ and Tsk2/+ mice was mapped to human orthologs and compared to SSc skin biopsy-derived gene expression.

系统性硬化症（Systemic sclerosis, SSc）因显著的疾病异质性而极具研究复杂性。目前尚未有能够在分子层面重现该疾病不同亚型的系统性硬化症动物模型被明确阐明。本研究针对多种系统性硬化症小鼠模型与患者的基因组数据开展跨物种比较分析，旨在明确哪些动物模型能够最精准地反映系统性硬化症固有的基因表达亚型。研究将硬皮病样移植物抗宿主病小鼠、博莱霉素诱导纤维化小鼠以及Tsk1/+、Tsk2/+小鼠的皮肤组织基因表达数据映射至人类同源基因，并与系统性硬化症皮肤活检样本的基因表达数据进行对比分析。