The tight skin 2 mouse: An animal model of scleroderma displaying cutaneous fibrosis and mononuclear cell infiltration
The tight skin 2 mouse: An animal model of scleroderma displaying cutaneous fibrosis and mononuclear cell infiltration
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DOI：
10.1002/art.1780381212
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发表时间：
1995-12-01
影响因子：
--
通讯作者：
Jimenez, SA
中科院分区：
文献类型：
--
作者：
Christner, PJ;Peters, J;Jimenez, SA
目标。描述一种表型特征类似于系统性硬化症(SSC)的突变Tsk2/+小鼠皮肤的组织病理学和生化特征，并报告Tsk2基因座的初步遗传图谱。对Tsk2/+小鼠和正常小鼠皮肤活检标本进行组织学检查，并测定胶原含量和I型胶原信使核糖核酸(I型胶原信使RNA)水平。亚种间回交是确定Tsk2基因座在小鼠1号染色体上位置的第一步。Tsk2/+小鼠皮肤的组织学检查显示真皮和脂肪组织中有明显的胶原积聚和单核细胞浸润，生化研究显示Tsk2/+小鼠皮肤的胶原含量增加，α1(I)前胶原mRNA的稳态水平升高。Tsk2基因定位于小鼠1号染色体上15.3-centimorgan区间。Tsk2是一种新的突变，它表现出类似于SSc患者皮肤的组织病理学和生化异常，包括胶原含量增加和I型胶原基因的表达，该突变已被定位在小鼠1号染色体上15.3 cM的区域。对该新突变的进一步研究将有助于确定先前未描述的正常和病理性胶原基因表达的调节机制。
Objective. To describe the histopathologic and biochemical characteristics of skin from the Tsk2/+ mouse, a mutation with phenotypic features resembling those of systemic sclerosis (SSc), and to report the initial genetic mapping of the Tsk2 locus.Methods. Histologic examination was performed and collagen content and type I collagen messenger RNA (mRNA) levels were determined in skin biopsy specimens from Tsk2/+ mice and normal mice. An inter-subspecific backcross was conducted as a first step toward identifying the position of the Tsk2 locus on mouse chromosome 1.Results. Histologic examination of Tsk2/+ mouse skin revealed marked accumulation of collagen and infiltration with mononuclear cells in the dermis and adipose tissue, Biochemical studies of Tsk2/+ mouse skin showed increased collagen content and elevated steady-state levels of alpha 1(I) procollagen mRNA. Tsk2 was mapped to a 15.3-centimorgan interval on mouse chromosome 1.Conclusion. Tsk2 is a novel mutation which displays histopathologic and biochemical abnormalities similar to those present in the skin of patients with SSc, including increased collagen content and expression of type I collagen genes, This mutation has been mapped to a 15.3-cM region on mouse chromosome 1. Further study of this novel mutation will allow the identification of previously undescribed mechanisms involved in the regulation of normal and pathologic collagen gene expression.