Efficient breeding system of infertile Niemann–Pick disease type C model mice by in vitro fertilization and embryo transfer

Niemann-Pick disease type C (NPC) is a lethal genetic disease with mutations in <i>NPC1</i> or <i>NPC2</i> gene. <i>Npc1</i>-deficient (<i>Npc1</i>^-/-) mice have been used as a model for NPC pathogenesis to develop novel therapies for NPC. However, <i>Npc1</i>^-/- 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 <i>Npc1</i>^-/- mice. Fertilized oocytes were also obtained via IVF using cryopreserved sperm from <i>Npc1</i>^-/- 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 <i>Npc1</i>^-/- mice and will contribute to developing novel therapeutic methods using NPC model mice.