Ectopic expression of BBS1 rescues male infertility, but not retinal degeneration, in a BBS1 mouse model

Bardet-Biedl syndrome (BBS) is a rare ciliopathy for which there are no current effective treatments. BBS is a genetically heterogeneous disease, though the M390R mutation in BBS1 is involved in approximately 25% of all genetic diagnoses of BBS. The principle features of BBS include retinal degeneration, obesity, male infertility, polydactyly, intellectual disability, and renal abnormalities. Patients with mutations in BBS genes often present with night blindness within the first decade of life, which progresses to complete blindness. This is due to progressive loss of photoreceptor cells. Male infertility is caused by a lack of spermatozoa flagella, rendering them immobile. In this study, we have crossed the wild-type human BBS1 gene, driven by the CAG promoter, onto the Bbs1M390R/M390R mouse model to determine if ectopic expression of BBS1 rescues male infertility and retinal degeneration. qRT-PCR indicates that the BBS1 transgene is expressed in multiple tissues throughout the mouse,...巴德特-比德尔综合征（Bardet-Biedl syndrome, BBS）是一种罕见的纤毛病（ciliopathy），目前尚无有效治疗手段。BBS属于遗传性异质性疾病，其中BBS1基因的M390R突变约占BBS所有基因确诊病例的25%。该疾病的主要临床特征包括视网膜变性、肥胖、男性不育、多指（趾）症、智力障碍及肾脏异常。携带BBS基因突变的患者通常在10岁前出现夜盲症，病情会逐步进展为全盲，这一过程源于感光细胞的进行性丢失。男性不育症由精子鞭毛缺失引发，导致精子无法运动。本研究中，我们将由CAG启动子（CAG promoter）驱动的野生型人源BBS1基因，转入Bbs1M390R/M390R小鼠模型，以探究BBS1的异位表达是否能够挽救男性不育与视网膜变性。实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction, qRT-PCR）结果显示，BBS1转基因在小鼠的多种组织中均有表达，……