COLLAGENASE EXPRESSION IN THE LUNGS OF TRANSGENIC MICE CAUSES PULMONARY-EMPHYSEMA
COLLAGENASE EXPRESSION IN THE LUNGS OF TRANSGENIC MICE CAUSES PULMONARY-EMPHYSEMA
复制标题
DOI：
10.1016/0092-8674(92)90391-o
复制
发表时间：
1992-12-11
期刊：
影响因子：
64.5
通讯作者：
CHADA, K
中科院分区：
文献类型：
--
作者：
DARMIENTO, J;DALAL, SS;CHADA, K
在触珠蛋白启动子的引导下，产生了在肺中表达人胶原酶转基因的转基因小鼠。组织学分析显示肺泡壁破坏和肺泡间隙合并，无纤维化或炎症的证据。这种病理与在人类肺气肿中观察到的形态学变化惊人地相似，因此暗示间质胶原酶在疾病过程中可能是一种病因。虽然弹性蛋白酶被认为是肺气肿肺损伤的主要酶，但本研究提供了其他细胞外基质蛋白酶在肺气肿中发挥作用的证据。此外，这些转基因小鼠是研究肺气肿发病机制的一个明确的遗传动物模型系统。
Transgenic mice were generated that expressed a human collagenase transgene in their lungs under the direction of the haptoglobin promoter. Histological analysis demonstrated disruption of the alveolar walls and coalescence of the alveolar spaces with no evidence of fibrosis or inflammation. This pathology is strikingly similar to the morphological changes observed in human emphysema and therefore implicates interstitial collagenase as a possible etiological agent in the disease process. Although elastase has been proposed as the primary enzyme responsible for emphysematous lung damage, this study provides evidence that other extracellular matrix proteases could play a role in emphysema. In addition, these transgenic mice are a defined genetic animal model system to study the pathogenesis of emphysema.