Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2011 Apr 4;6(4):e18266. doi: 10.1371/journal.pone.0018266.
Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.
开发合适的小鼠模型将有助于研究人类银屑病的发病机制，并有助于开发治疗方法。然而，尽管已经提出了许多银屑病小鼠模型，但没有一种模型能够重现人类疾病的所有特征，并且也没有广泛应用银屑病小鼠模型的标准化验证标准。在这项研究中，我们使用全基因组转录谱分析来比较人类银屑病皮损的基因表达模式与五种银屑病小鼠模型（K5-Tie2、咪喹莫特、K14-AREG、K5-Stat3C 和 K5-TGFβ1）中发生的基因表达模式。虽然与每种小鼠表型相关的皮肤基因表达谱与人类银屑病的表达谱具有统计学显著相似性，但与人类银屑病相比，每种模型都显示出独特的相似性和差异性。对于所有五种模型，与表皮发育和角化相关的基因均与人类疾病具有很强的对应关系。相比之下，免疫和炎症相关基因的表达在不同模型之间的差异比人类疾病更为多变。这些发现支持所有五种模型作为研究工具的价值，每个模型都有可识别的与人类疾病趋同和趋异的区域。此外，本文中使用的方法为评估拟议的银屑病小鼠模型提供了一种客观和定量的方法，可在未来的研究中战略性地应用，以评估小鼠表型相对于人类银屑病特定方面的优势。
