LUNG-DISEASE IN THE CYSTIC-FIBROSIS MOUSE EXPOSED TO BACTERIAL PATHOGENS
LUNG-DISEASE IN THE CYSTIC-FIBROSIS MOUSE EXPOSED TO BACTERIAL PATHOGENS
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DOI：
10.1038/ng0495-351
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发表时间：
1995-04-01
期刊：
影响因子：
30.8
通讯作者：
PORTEOUS, DJ
中科院分区：
文献类型：
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作者：
DAVIDSON, DJ;DORIN, JR;PORTEOUS, DJ
肺部疾病是囊性纤维化（CF）死亡的主要原因，但没有证据表明出生时明显的肺部受累。我们在这里表明，同样的情况也适用于基因靶向cftr（m1HGU）突变小鼠。此外，该CF小鼠模型显示清除金黄色葡萄球菌和洋葱伯克霍尔德氏菌（假单胞菌）的能力受损，这两种机会性肺病原体与CF受试者的肺部疾病密切相关。cftr（m1HGU）纯合子显示粘液潴留和坦率的肺部疾病，以响应重复的微生物暴露。因此，cftr（m1HGU）小鼠中的肺部疾病响应于细菌感染而发展，建立了一个模型来剖析CF肺部疾病的发病机制，并提供了一个临床相关的终点来评估药理学或遗传干预的疗效。
Lung disease is the major cause of death in cystic fibrosis (CF), but there is no evidence for overt lung involvement at birth. We show here that the same is true for the gene targeted cftr(m1HGU) mutant mouse. Furthermore, this CF mouse model demonstrates an impaired capacity to clear Staphylococcus aureus and Burkholderia (Pseudomonas) cepacia, two opportunistic lung pathogens closely associated with lung disease in CF subjects. The cftr(m1HGU) homozygotes display mucus retention and frank lung disease in response to repeated microbial exposure. Thus, lung disease in the cftr(m1HGU) mouse develops in response to bacterial infection, establishing a model to dissect the pathogenesis of CF pulmonary disease and providing a clinically relevant end point to assess the efficacy of pharmacologic or genetic interventions.