Inhibition of skin development by overexpression of transforming growth factor beta 1 in the epidermis of transgenic mice.
Inhibition of skin development by overexpression of transforming growth factor beta 1 in the epidermis of transgenic mice.
复制标题
转基因小鼠表皮过度表达转化生长因子β1抑制皮肤发育。
DOI：
10.1073/pnas.90.11.5237
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发表时间：
1993
影响因子：
11.1
通讯作者：
Roop,DR
中科院分区：
文献类型：
--
作者：
Sellheyer,K;Bickenbach,JR;Rothnagel,JA;Bundman,D;Longley,MA;Krieg,T;Roche,NS;Roberts,AB;Roop,DR
为了评估转化生长因子β 1在体内对皮肤的影响，我们将其靶向表达到转基因小鼠的表皮。为了确保活性tgf - β 1的表达，我们使用了具有Cys-223- >Ser和Cys-225- >Ser突变的猪tgf - β 1 cDNA，这两种突变允许构成激活。表达突变型转化生长因子β 1转基因的小鼠在出生时表现出显著的表型。皮肤非常有光泽，紧绷。这些动物很僵硬，移动和呼吸的能力似乎受到限制；死亡发生在24小时内。组织学上，皮肤最突出的特征是致密的正角化过度和毛囊数量减少。用5-溴脱氧尿苷进行的脉冲标记研究表明，表皮和毛囊中复制细胞的数量明显减少。因此，这些小鼠的宏观和微观外观，以及它们的新生儿死亡率，很可能是由于转化生长因子β 1的过度表达抑制了正常皮肤发育和抑制上皮细胞增殖。
To assess the effect of transforming growth factor beta 1 on the skin in vivo, we have targeted its expression to the epidermis of transgenic mice. To ensure that active TGF-beta 1 was expressed, we used a porcine TGF-beta 1 cDNA with mutations of Cys-223-->Ser and Cys-225-->Ser, which allow constitutive activation. Mice expressing the mutant transforming growth factor beta 1 transgene exhibited a marked phenotype at birth. The skin was very shiny and tautly stretched. These animals were rigid and appeared to be restricted in their ability to move and breathe; death occurred within 24 hr. Histologically, the most prominent features of the skin were a compact orthohyperkeratosis and a reduction in the number of hair follicles. Pulse-labeling studies with 5-bromodeoxyuridine demonstrated a marked reduction in the number of replicating cells in the epidermis and hair follicles. Thus, the macro- and microscopic appearance of these mice, as well as their neonatal lethality, most likely result from inhibition of normal skin development and suppression of epithelial cell proliferation by the overexpression of transforming growth factor beta 1.