Identification of gene mutations associated with the phenotype of short-limb mice emerging from a foundation colony of severely immunodeficient mice.

Here, we report the identification of causative genes for limb-shortening in individuals repeatedly found in a population of severely immunodeficient NOG mice maintained via sibling mating. First, we conducted a pedigree survey to determine whether limb-shortening was a recessive genetic trait and then identified it using a crossing test. Simultaneously, the symptoms were identified in detail using pathological analysis.

Establishment of a human microbiome- and immune system-reconstituted dual-humanized mouse model.

Humanized mice are widely used to study the human immune system in vivo and investigate therapeutic targets for various human diseases. Immunodeficient NOD/Shi-scid-IL2rγ (NOG) mice transferred with human hematopoietic stem cells are a useful model for studying human immune systems and analyzing engrafted human immune cells. The gut microbiota plays a significant role in the development and function of immune cells and the maintenance of immune homeostasis; however, there is currently no available animal model that has been reconstituted with human gut microbiota and immune systems in vivo.

Improved engraftment of human peripheral blood mononuclear cells in NOG MHC double knockout mice generated using CRISPR/Cas9.

Humanized mice are widely used to study the human immune system in vivo and develop therapies for various human diseases. Human peripheral blood mononuclear cells (PBMC)-engrafted NOD/Shi-scid IL2rγ (NOG) mice are useful models for characterization of human T cells. However, the development of graft-versus-host disease (GVHD) limits the use of NOG PBMC models.

Creation of an experimental rearing environment for microbiome animal research using an individually ventilated cage system and bioBUBBLE enclosure.

To avoid microbial contamination risk, vinyl film isolators are generally used in animal microbiome experiments involving germ-free (GF) mice and/or gnotobiotic (GB) mice. However, it can take several months to gain expertise in operating the isolator competently. Furthermore, sterilization and sterility testing, which are essential for isolator preparation, can take more than 20 days.

Study on AAV-mediated gene therapy for diabetes in humanized liver mouse to predict efficacy in humans.

Most in vivo studies on the conversion to insulin-producing cells with AAV carrying PDX1 gene are performed in rodents. However, there is little information regarding Adeno-associated virus (AAV) carrying PDX1 gene transduced to human liver in vivo because accidental death caused by unpredicted factors cannot be denied, such as the hypoglycemic agent troglitazone with hepatic failure. Here we aim to confirm insulin secretion from human liver transduced with AAV carrying PDX1 gene in vivo and any secondary effect using a humanized liver mouse.