Key Laboratory of Animal Biotechnology, the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
PLoS One. 2013 Jun 17;8(6):e65869. doi: 10.1371/journal.pone.0065869. Print 2013.
Folliculin (FLCN) is a conserved tumor suppressor gene whose loss is associated with the human Birt-Hogg-Dubé (BHD) syndrome. However, its molecular functions remain largely unknown. In this work, we generated a Drosophila BHD model through genomic deletion of the FLCN gene (DBHD(-) ). The DBHD mutant larvae grew slowly and stopped development before pupation, displaying various characteristics of malnutrition. We found the growth delay was sensitive to the nutrient supplies. It became more severe upon restrictions of the dietary yeast; while high levels of yeast significantly restored the normal growth, but not viability. We further demonstrated that leucine was able to substitute for yeast to provide similar rescues. Moreover, the human FLCN could partially rescue the DBHD(-) phenotypes, indicating the two genes are involved in certain common mechanisms. Our work provides a new animal model of the BHD syndrome and suggests that modulation of the local nutrient condition might be a potential treatment of the BHD lesions.
卵泡抑素 (FLCN) 是一种保守的抑癌基因，其缺失与人类 Birt-Hogg-Dubé (BHD) 综合征有关。然而，其分子功能在很大程度上仍然未知。在这项工作中，我们通过基因组缺失 FLCN 基因 (DBHD(-)) 生成了一个果蝇 BHD 模型。DBHD 突变幼虫生长缓慢，在蛹化前停止发育，表现出各种营养不良的特征。我们发现生长延迟对营养供应敏感。当限制饮食中的酵母时，它变得更加严重；而高水平的酵母则显著恢复了正常生长，但不能恢复活力。我们进一步表明亮氨酸能够替代酵母提供类似的拯救。此外，人类 FLCN 可以部分挽救 DBHD(-) 表型，表明这两个基因涉及某些共同的机制。我们的工作提供了 BHD 综合征的一种新的动物模型，并表明调节局部营养条件可能是治疗 BHD 病变的一种潜在方法。
