Abstract:
Niemann-Pick disease type C (NPC) is a lethal genetic disease with mutations in NPC1 or NPC2 gene. Npc1-deficient (Npc1-/-) mice have been used as a model for NPC pathogenesis to develop novel therapies for NPC. However, Npc1-/- mice are infertile; thus, securing sufficient numbers for translational research is difficult. Hence, we attempted reproductive engineering techniques such as in vitro fertilization (IVF) and sperm cryopreservation. For the first time, we succeeded in producing fertilized oocytes via IVF using male and female Npc1-/- mice. Fertilized oocytes were also obtained via IVF using cryopreserved sperm from Npc1-/- mice. The obtained fertilized oocytes normally developed into live pups via embryo transfer, and they eventually exhibited NPC pathogenesis. These findings are useful for generating an efficient breeding system that overcomes the reproductive challenges of Npc1-/- mice and will contribute to developing novel therapeutic methods using NPC model mice.
摘要:
尼曼-匹克病C型(NPC)是NPC1或NPC2基因突变的致死性遗传病。Npc1缺陷(Npc1-/-)小鼠已被用作NPC发病机理的模型,以开发针对NPC的新疗法。然而,Npc1-/-小鼠不育;因此,为转化研究确保足够的数量是困难的。因此,我们尝试了生殖工程技术,例如体外受精(IVF)和精子冷冻保存。第一次,我们使用雄性和雌性Npc1-/-小鼠通过IVF成功产生了受精的卵母细胞。还使用来自Npc1-/-小鼠的冷冻保存的精子通过IVF获得受精的卵母细胞。获得的受精卵母细胞通常通过胚胎移植发育成活的幼崽,他们最终表现出NPC的发病机制。这些发现对于产生克服Npc1-/-小鼠的生殖挑战的有效育种系统是有用的,并且将有助于开发使用NPC模型小鼠的新型治疗方法。