Matriptase-deficient mice exhibit ichthyotic skin with a selective shift in skin microbiota.
Matriptase-deficient mice exhibit ichthyotic skin with a selective shift in skin microbiota.
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基质酶缺陷小鼠表现出鱼鳞病皮肤，并伴有皮肤微生物群的选择性变化。
DOI：
10.1038/jid.2009.104
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Segre,JuliaA
中科院分区：
文献类型：
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作者：
Scharschmidt,TiffanyC;List,Karin;Grice,ElizabethA;Szabo,Roman;NISCComparativeSequencingProgram;Renaud,Gabriel;Lee,Chyi-ChiaR;Wolfsberg,TyraG;Bugge,ThomasH;Segre,JuliaA
肿瘤发生抑制因子14（St 14）编码间质蛋白酶（matriptase），一种丝氨酸蛋白酶，其在体内调节聚丝蛋白原加工成聚丝蛋白。在这里，我们报告说，转基因小鼠与野生型St 14水平的1%（St 14 hypo/-）显示异常加工的原丝聚蛋白和模型人类鱼鳞病皮肤表型。1周龄时皮肤出现鳞屑，伴有潜在的表皮棘皮症和角化过度以及CD 4 + T细胞真皮浸润。当暴露于出生后环境时，抗微生物肽的上调发生。对细菌16 S rRNA基因进行直接基因组测序以查询微生物多样性，发现St 14 hypo/-小鼠和对照同窝小鼠之间的生殖和群落结构都发生了显著变化。St 14 hypo/-小鼠在皮肤微生物群中具有选择性变化，皮肤细菌的优势属减少，假单胞菌以及伴随的棒状杆菌和链球菌的增加。St 14 hypo/-小鼠提供的早期证据表明，皮肤微生物组可以通过遗传状态进行特异性改变，这可能在调节皮肤疾病方面发挥重要作用。
Suppressor of tumorigenicity 14 (St14) encodes matriptase, a serine protease, which regulates processing of profilaggrin to filagginin vivo. Here, we report that transgenic mice with 1% of wild-typeSt14levels (St14hypo/-) display aberrant processing of profilaggrin and model human ichthyotic skin phenotypes. Scaling of the skin appears at 1 week of age with underlying epidermal acanthosis and orthohyperkeratosis as well as a CD4+ T-cell dermal infiltrate. Upregulation of antimicrobial peptides occurs when challenged by exposure to the postnatal environment. Direct genomic sequencing of bacterial 16S rRNA genes to query microbial diversity identifies a significant shift in both phylogeny and community structure betweenSt14hypo/-mice and control littermates.St14hypo/-mice have a selective shift in resident skin microbiota with a decrease of the dominant genus of skin bacteria,Pseudomonasand an accompanying increase ofCorynebacteriumandStreptococcus.St14hypo/-mice provide early evidence that the cutaneous microbiome can be specifically altered by genetic state, which may play an important role in modulating skin disease.