Polygenic mouse model of psoriasiform skin disease in CD18-deficient mice
Polygenic mouse model of psoriasiform skin disease in CD18-deficient mice
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DOI：
10.1073/pnas.93.5.2116
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发表时间：
1996-03-05
影响因子：
11.1
通讯作者：
Beaudet, AL
中科院分区：
文献类型：
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作者：
Bullard, DC;ScharffetterKochanek, K;Beaudet, AL
以前，通过基因靶向产生了CD 18的亚型突变，纯合子小鼠表现出循环中性粒细胞计数增加、对化学诱导的腹膜炎的反应缺陷和移植排斥延迟。当该突变与PL/J近交系回交时，几乎所有纯合子小鼠都表现出慢性炎性皮肤病，平均发病年龄为出生后11周，该疾病的特征是红斑、脱发以及鳞屑和结痂的发展。组织病理学显示表皮增生、角膜下微肿胀、角化过度、角化不全和淋巴细胞胞吐，这些是人类银屑病和其他过度增殖性炎性皮肤病的共同特征，重复培养未能证明细菌或真菌微生物可能参与这种疾病的发病机制，皮下注射地塞米松后皮炎迅速消退。纯合子突变小鼠在a（PL/J x C57 BL/6 J）F-1背景没有发生疾病，回交实验表明少数基因（也许是一分为一），除了CD 18，决定易感性的疾病，这种表型提供了一个模型，炎症性皮肤病，可能有一般相关性的多基因人类炎症性疾病，并且应该有助于识别在炎症过程中与β 2整合素相互作用的基因。
Previously, a hypomorphic mutation in CD18 was generated by gene targeting, with homozygous mice displaying increased circulating neutrophil counts, defects in the response to chemically induced peritonitis, and delays in transplantation rejection, When this mutation was backcrossed onto the PL/J inbred strain, virtually all homozygous mice del eloped a chronic inflammatory skin disease with a mean age of onset of 11 weeks after birth, The disease was characterized by erythema, hair loss, and the development of scales and crusts, The histopathology revealed hyperplasia of the epidermis, subcorneal microabscesses, orthohyperkeratosis, parakeratosis, and lymphocyte exocytosis, which are features in common with human psoriasis and other hyperproliferative inflammatory skin disorders, Repetitive cultures failed to demonstrate bacterial or fungal organisms potentially involved in the pathogenesis of this disease, and the dermatitis resolved rapidly after subcutaneous administration of dexamethasone. Homozygous mutant mice on a (PL/J x C57BL/6J) F-1 background did not develop the disease and backcross experiments suggest that a small number of genes (perhaps as fen as one), In addition to CD18, determine susceptibility to the disorder, This phenotype provides a model for inflammatory skin disorders, may have general relevance to polygenic human inflammatory diseases, and should help to identify genes that interact with the beta(2) integrins in inflammatory processes.